Is AGAP1 p.Val255Ile (c.763G>A) pathogenic?

AGAP1 p.Val255Ile (c.763G>A) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-23). AlphaMissense: likely benign (0.0804); Very rare (popmax 0.00666%, afr).

How common is AGAP1 p.Val255Ile (c.763G>A) in the general population?

AGAP1 p.Val255Ile (c.763G>A) is very rare (popmax 0.00666%, afr) (gnomAD).

What do computational predictors say about AGAP1 p.Val255Ile (c.763G>A)?

AlphaMissense predicts likely benign (score 0.0804) — an in-silico prediction, not a clinical call.

AGAP1 p.Val255Ile

c.763G>A · rs367742479 · VCV2970465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0804 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0804	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -10.74	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00666% African / African-American · 5/75,044 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00198% 32/1,614,190 alleles · very rare exomes 29/1,461,890 · genomes 3/152,300 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00666%	15,009
South Asian	0.0022%	45,544
European (non-Finnish)	0.00203%	49,168
Remaining individualsnot grpmax-eligible	0.0016%	62,510

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AGAP1
Protein: p.Val255Ile
Coding: c.763G>A
MANE Select: NM_001037131
dbSNP: rs367742479
Type: single nucleotide variant
Location: chr2:235797848 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 255: the 'small gtpase-like' region

Full AGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/agap1-p-val255ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown