PRAMEF1

Chr 1

PRAME family member 1

NCBI Gene: 65121 ENSG00000116721 UniProt: O95521 OMIM: 621623

PRAMEF1 encodes a protein that belongs to the PRAME gene family and may function in reproductive tissues during development. This gene is extremely intolerant to loss-of-function variants (pLI near 0), but no definitive human disease associations have been established in the provided data. The clinical significance of PRAMEF1 variants in pediatric neurological disorders remains unclear based on current evidence.

OMIM ResearchSummary from RefSeq

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.88

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.88LOEUF

pLI 0.000

Z-score -1.03

OE 1.35 (0.88–1.88)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.13Z-score

OE missense 1.39 (1.27–1.52)

326 obs / 234.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.35 (0.88–1.88)

0≤0.351.4

Missense OE?1.39 (1.27–1.52)

0≤0.61.4

Synonymous OE?1.43

0≤1.21.6

LoF obs/exp: 14 / 10.4Missense obs/exp: 326 / 234.2Syn Z: -3.35

Background carrier burden — how many people carry a rare variant somewhere in PRAMEF1?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 36

581 rare PASS variants

Rare truncating (LoF)

1 in 1,100

50 rare PASS variants

Rare synonymous (reference)

1 in 84

239 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRAMEF1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 57	1 in 1,900
South Asian	~43k	1 in 41	1 in 1,200
Remaining (unassigned)	~30k	1 in 41	1 in 400
European (Finnish)	~27k	1 in 160	1 in 1,500
Admixed American	~22k	1 in 43	1 in 1,500
African / African American	~21k	1 in 32	1 in 910
East Asian	~20k	1 in 39	1 in 1,300
Ashkenazi Jewish	~13k	1 in 580	none seen
Middle Eastern	~2,880	1 in 43	≈ 1 in 1,200

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓