Is AGAP1 p.Val307Ile (c.919G>A) pathogenic?

AGAP1 p.Val307Ile (c.919G>A) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-30). AlphaMissense: likely benign (0.0933); Very rare (popmax 0.00439%, sas).

How common is AGAP1 p.Val307Ile (c.919G>A) in the general population?

AGAP1 p.Val307Ile (c.919G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about AGAP1 p.Val307Ile (c.919G>A)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

AGAP1 p.Val307Ile

c.919G>A · rs767939918 · VCV2717204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -10.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.6	GERP 0.95, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	22.4	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 0.00439% South Asian · 4/91,074 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00173% 28/1,614,066 alleles · very rare exomes 26/1,461,880 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,769
Admixed American	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0032%	31,242
East Asian	0.00223%	44,890
European (non-Finnish)	0.00153%	65,558
African / African-American	0.00133%	74,936

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.Val307Ile
Coding: c.919G>A
MANE Select: NM_001037131
dbSNP: rs767939918
Type: single nucleotide variant
Location: chr2:235799484 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 307: the 'disordered' 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-val307ile (accessed [today's date]).

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