Is AGAP5 p.Phe113Val (c.337T>G) pathogenic?

AGAP5 p.Phe113Val (c.337T>G) is classified Uncertain significance in AGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.3238); Ultra-rare (popmax 0.0396%, sas).

How common is AGAP5 p.Phe113Val (c.337T>G) in the general population?

AGAP5 p.Phe113Val (c.337T>G) is ultra-rare (popmax 0.0396%, sas) (gnomAD).

What do computational predictors say about AGAP5 p.Phe113Val (c.337T>G)?

AlphaMissense predicts likely benign (score 0.3238) — an in-silico prediction, not a clinical call.

AGAP5 p.Phe113Val

c.337T>G · VCV4249898

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3238 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0396%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3238	likely benign
REVEL	0.414	indeterminate
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 14 kb · p 6.4e-07 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0396% South Asian · 36/90,998 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00288% 46/1,598,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0396%	2,528
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,932
Remaining individualsnot grpmax-eligible	0.00642%	15,568

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: AGAP5
Protein: p.Phe113Val
Coding: c.337T>G
MANE Select: NM_001144000
Type: single nucleotide variant
Location: chr10:73694760 (GRCh38)
Gene constraint: LOEUF 0.717 · pLI 0.47 (gnomAD)
Structure: AlphaFold pLDDT 62.80

Full AGAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP5 p.Phe113Tyr Uncertain significance ★ ⚠ same residue
AGAP5 p.Ala195Val Uncertain significance ★ ⚠ same type
AGAP5 p.Ala397Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala41Glu Uncertain significance ★ ⚠ same type
AGAP5 p.Ala43Val Uncertain significance ★ ⚠ same type
AGAP5 p.Ala444Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala596Thr Uncertain significance ★ ⚠ same type
AGAP5 p.Ala608Thr 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/agap5-p-phe113val (accessed [today's date]).

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