Is AGAP1 p.Ala809Ser (c.2425G>T) pathogenic?

AGAP1 p.Ala809Ser (c.2425G>T) is classified Uncertain significance in AGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-06). AlphaMissense: likely benign (0.2996); Ultra-rare (popmax 0.0213%, afr).

How common is AGAP1 p.Ala809Ser (c.2425G>T) in the general population?

AGAP1 p.Ala809Ser (c.2425G>T) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about AGAP1 p.Ala809Ser (c.2425G>T)?

AlphaMissense predicts likely benign (score 0.2996) — an in-silico prediction, not a clinical call.

AGAP1 p.Ala809Ser

c.2425G>T · VCV4248976

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2996 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2996	likely benign
REVEL	0.675	pathogenic-leaning
SaProt	LLR -12.35	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 75 kb · p 0.03 · regional, not allelic
Overall
CADD	28.9	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 0.0213% African / African-American · 16/75,028 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00136% 22/1,613,894 alleles · ultra-rare exomes 9/1,461,628 · genomes 13/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,689
Admixed American	0.00666%	15,005
Remaining individualsnot grpmax-eligible	0.0016%	62,492
South Asian	0.0011%	91,070

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.Ala809Ser
Coding: c.2425G>T
MANE Select: NM_001037131
Type: single nucleotide variant
Location: chr2:236123973 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB

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

Similar variants

AGAP1 p.Ala418Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala52Ser Uncertain significance ★★ ⚠ same type
AGAP1 p.Ala570Gly Uncertain significance ★★ same type
AGAP1 p.Arg14Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg313His Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg696Trp Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg770Cys Uncertain significance ★★ ⚠ same type
AGAP1 p.Arg798Gln Uncertain significance ★★ ⚠ same type

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-ala809ser (accessed [today's date]).

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