GRAMD2A

Chr 15

GRAM domain containing 2A

Also known as: GRAMD2

NCBI Gene: 196996 ENSG00000175318 UniProt: Q8IUY3 OMIM: 620181

Enables phosphatidylinositol binding activity and phosphatidylinositol-4,5-bisphosphate binding activity. Involved in endoplasmic reticulum-plasma membrane tethering and regulation of store-operated calcium entry. Located in endoplasmic reticulum membrane; organelle membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.000

Z-score 0.28

OE 0.93 (0.66–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.96Z-score

OE missense 0.80 (0.70–0.92)

149 obs / 185.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.93 (0.66–1.36)

0≤0.351.4

Missense OE?0.80 (0.70–0.92)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 20 / 21.4Missense obs/exp: 149 / 185.8Syn Z: 1.41

Background carrier burden — how many people carry a rare variant somewhere in GRAMD2A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

451 rare PASS variants

Rare truncating (LoF)

1 in 1,300

84 rare PASS variants

Rare synonymous (reference)

1 in 270

145 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for GRAMD2A. 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 150	1 in 1,800
South Asian	~43k	1 in 110	1 in 490
Remaining (unassigned)	~30k	1 in 97	1 in 1,400
European (Finnish)	~27k	1 in 1,100	1 in 4,900
Admixed American	~22k	1 in 150	1 in 550
African / African American	~21k	1 in 130	1 in 740
East Asian	~20k	1 in 140	1 in 460
Ashkenazi Jewish	~13k	1 in 290	1 in 2,600
Middle Eastern	~2,884	1 in 120	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 11 of 12 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 12.? see exons ↓