Is AGAP4 p.Met248Val (c.742A>G) pathogenic?

AGAP4 p.Met248Val (c.742A>G) is classified Uncertain significance in AGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-27). AlphaMissense: likely benign (0.0687); Rare (popmax 0.829%, afr).

How common is AGAP4 p.Met248Val (c.742A>G) in the general population?

AGAP4 p.Met248Val (c.742A>G) is rare (popmax 0.829%, afr) (gnomAD).

What do computational predictors say about AGAP4 p.Met248Val (c.742A>G)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

AGAP4 p.Met248Val

c.742A>G · rs782252245 · VCV2393118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.829%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	phastCons 0.019
Regional constraint	o/e 0.32	constrained · MANE · 20 kb · p 3.3e-32 · regional, not allelic
Overall
CADD	14.54	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M225V vs ClinVar M248V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.829% African / African-American · 459/55,344 alleles

Filtering AF 0.767% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.742%

Overall 0.373% 4,917/1,318,720 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.829%	121
Middle Eastern	0.423%	236
European (non-Finnish)	0.391%	256
South Asian	0.356%	281
Remaining individualsnot grpmax-eligible	0.305%	328
Admixed American	0.299%	334
Ashkenazi Jewishnot grpmax-eligible	0.156%	642
East Asian	0.101%	986
Finnishnot grpmax-eligible	0.0752%	1,330

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: AGAP4
Protein: p.Met248Val
Coding: c.742A>G
MANE Select: NM_001276343
dbSNP: rs782252245
Type: single nucleotide variant
Location: chr10:45827234 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 63.70
Residue 248: the 'disordered' region

Full AGAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP4 p.Ala41Thr Uncertain significance ★ ⚠ same type
AGAP4 p.Ala464Val Uncertain significance ★ ⚠ same type
AGAP4 p.Ala466Ser Uncertain significance ★ ⚠ same type
AGAP4 p.Ala627Val Uncertain significance ★ ⚠ same type
AGAP4 p.Ala640Val Uncertain significance ★ ⚠ same type
AGAP4 p.Ala655Val Uncertain significance ★ ⚠ same type
AGAP4 p.Arg137Leu Uncertain significance ★ ⚠ same type
AGAP4 p.Arg246Gln 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/agap4-p-met248val (accessed [today's date]).

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