Is ARFGAP1 p.Ser277Phe (c.830C>T) pathogenic?

ARFGAP1 p.Ser277Phe (c.830C>T) is classified Uncertain significance in ARFGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-23). AlphaMissense: likely benign (0.169); Ultra-rare (popmax 0.0535%, eas).

How common is ARFGAP1 p.Ser277Phe (c.830C>T) in the general population?

ARFGAP1 p.Ser277Phe (c.830C>T) is ultra-rare (popmax 0.0535%, eas) (gnomAD).

What do computational predictors say about ARFGAP1 p.Ser277Phe (c.830C>T)?

AlphaMissense predicts likely benign (score 0.169) — an in-silico prediction, not a clinical call.

ARFGAP1 p.Ser277Phe

c.830C>T · rs746605629 · VCV2522253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.169 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.169	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.43, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 11 kb · p 0.56 · regional, not allelic
Overall
CADD	22.6	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 0.0535% East Asian · 24/44,882 alleles

Filtering AF 0.0368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00161% 26/1,613,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0535%	1,870
Remaining individualsnot grpmax-eligible	0.0016%	62,504
South Asian	0.0011%	91,088

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.Ser277Phe
Coding: c.830C>T
MANE Select: NM_018209
dbSNP: rs746605629
Type: single nucleotide variant
Location: chr20:63285709 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 61.90 · 2 PDB

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

Similar variants

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
ARFGAP1 p.Ala352Thr 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-ser277phe (accessed [today's date]).

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