Is ARFGAP3 p.Ile510Val (c.1528A>G) pathogenic?

ARFGAP3 p.Ile510Val (c.1528A>G) is classified Uncertain significance in ARFGAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: ambiguous (0.3501); Very rare (popmax 0.00549%, sas).

How common is ARFGAP3 p.Ile510Val (c.1528A>G) in the general population?

ARFGAP3 p.Ile510Val (c.1528A>G) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about ARFGAP3 p.Ile510Val (c.1528A>G)?

AlphaMissense predicts ambiguous (score 0.3501) — an in-silico prediction, not a clinical call.

ARFGAP3 p.Ile510Val

c.1528A>G · rs769244778 · VCV2617337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3501 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Computational evidence

Protein change
AlphaMissense	0.3501	ambiguous
REVEL	0.295	indeterminate
SaProt	LLR -6.88	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 0.12, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 60 kb · p 0.79 · regional, not allelic
Overall
CADD	24.2	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 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000479% 7/1,461,826 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
European (non-Finnish)	0.000169%	589,995

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: ARFGAP3
Protein: p.Ile510Val
Coding: c.1528A>G
MANE Select: NM_014570
dbSNP: rs769244778
Type: single nucleotide variant
Location: chr22:42799044 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.12 · 1 PDB

Full ARFGAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFGAP3 p.Ala164Val Uncertain significance ★ ⚠ same type
ARFGAP3 p.Ala170Glu Uncertain significance ★ ⚠ same type
ARFGAP3 p.Ala234Thr Uncertain significance ★ ⚠ same type
ARFGAP3 p.Ala238Gly Uncertain significance ★ ⚠ same type
ARFGAP3 p.Ala262Thr Uncertain significance ★ ⚠ same type
ARFGAP3 p.Ala335Thr Uncertain significance ★ ⚠ same type
ARFGAP3 p.Ala426Ser Uncertain significance ★ ⚠ same type
ARFGAP3 p.Arg15Cys 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/arfgap3-p-ile510val (accessed [today's date]).

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