Is AGAP4 p.Asp18Val (c.53A>T) pathogenic?

AGAP4 p.Asp18Val (c.53A>T) is classified Uncertain significance in AGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.1532); Ultra-rare (popmax 0.0161%, afr).

How common is AGAP4 p.Asp18Val (c.53A>T) in the general population?

AGAP4 p.Asp18Val (c.53A>T) is ultra-rare (popmax 0.0161%, afr) (gnomAD).

What do computational predictors say about AGAP4 p.Asp18Val (c.53A>T)?

AlphaMissense predicts likely benign (score 0.1532) — an in-silico prediction, not a clinical call.

AGAP4 p.Asp18Val

c.53A>T · rs1361206615 · VCV3094182

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1532 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1532	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -5.87	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 1.5	phastCons 0.61
Regional constraint	o/e 0.32	constrained · MANE · 20 kb · p 3.3e-32 · regional, not allelic
Overall
CADD	15.88	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 0.0161% African / African-American · 12/74,310 alleles

Filtering AF 0.00928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00727%

Overall 0.00106% 17/1,596,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0161%	6,192
South Asian	0.0044%	22,732
Remaining individualsnot grpmax-eligible	0.00161%	62,220

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.Asp18Val
Coding: c.53A>T
MANE Select: NM_001276343
dbSNP: rs1361206615
Type: single nucleotide variant
Location: chr10:45847295 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 63.70

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-asp18val (accessed [today's date]).

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