Is AGAP1 p.Asp114Val (c.341A>T) pathogenic?

AGAP1 p.Asp114Val (c.341A>T) is classified Uncertain significance in AGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.9718); Rare (popmax 0.104%, sas).

How common is AGAP1 p.Asp114Val (c.341A>T) in the general population?

AGAP1 p.Asp114Val (c.341A>T) is rare (popmax 0.104%, sas) (gnomAD).

What do computational predictors say about AGAP1 p.Asp114Val (c.341A>T)?

AlphaMissense predicts likely pathogenic (score 0.9718) — an in-silico prediction, not a clinical call.

AGAP1 p.Asp114Val

c.341A>T · rs756920826 · VCV2203289

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9718 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.104%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9718	likely pathogenic
REVEL	0.704	pathogenic-leaning
SaProt	LLR -16.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 546 kb · p 0.00065 · regional, not allelic
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.104% South Asian · 95/91,082 alleles

Filtering AF 0.0873% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.081%

Overall 0.00737% 119/1,614,180 alleles · rare exomes 117/1,461,836 · genomes 2/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.104%	959
Middle Eastern	0.0495%	2,019
Admixed American	0.00833%	12,005
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.00127%	78,668

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.Asp114Val
Coding: c.341A>T
MANE Select: NM_001037131
dbSNP: rs756920826
Type: single nucleotide variant
Location: chr2:235740993 (GRCh38)
Gene constraint: LOEUF 0.366 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.01 · 2 PDB
Residue 114: the gld domain; 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-asp114val (accessed [today's date]).

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