Is ARFGAP1 p.Pro305Ser (c.913C>T) pathogenic?

ARFGAP1 p.Pro305Ser (c.913C>T) is classified Uncertain significance in ARFGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0592); Rare (popmax 0.114%, afr).

How common is ARFGAP1 p.Pro305Ser (c.913C>T) in the general population?

ARFGAP1 p.Pro305Ser (c.913C>T) is rare (popmax 0.114%, afr) (gnomAD).

What do computational predictors say about ARFGAP1 p.Pro305Ser (c.913C>T)?

AlphaMissense predicts likely benign (score 0.0592) — an in-silico prediction, not a clinical call.

ARFGAP1 p.Pro305Ser

c.913C>T · rs151256666 · VCV2617645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0592 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.114%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0592	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -5.67	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 0.35	GERP -2.8
Regional constraint	o/e 1.03	unconstrained · MANE · 11 kb · p 0.56 · regional, not allelic
Overall
CADD	3.5	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 0.114% African / African-American · 84/73,648 alleles

Filtering AF 0.0943% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0871%

Overall 0.00626% 99/1,581,452 alleles · rare exomes 53/1,429,226 · genomes 46/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.114%	877
South Asian	0.00782%	12,783
Remaining individualsnot grpmax-eligible	0.00658%	15,195
Admixed American	0.00535%	18,692
European (non-Finnish)	8.62e-05%	1,159,832

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: ARFGAP1
Protein: p.Pro305Ser
Coding: c.913C>T
MANE Select: NM_018209
dbSNP: rs151256666
Type: single nucleotide variant
Location: chr20:63287565 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 61.90 · 2 PDB
Residue 305: the 'disordered' region

Full ARFGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFGAP1 p.Pro305Leu Uncertain significance ★ ⚠ same residue
ARFGAP1 c.718-993C>T Uncertain significance ★ same type
ARFGAP1 p.Ala108Thr Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala158Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala236Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala240Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala255Val Uncertain significance ★ ⚠ same type
ARFGAP1 p.Ala27Thr 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/arfgap1-p-pro305ser (accessed [today's date]).

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