Is ARHGAP1 p.Leu263Phe (c.787C>T) pathogenic?

ARHGAP1 p.Leu263Phe (c.787C>T) is classified Benign in ARHGAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-02). AlphaMissense: ambiguous (0.4557); Low-frequency (popmax 2.19%, sas).

How common is ARHGAP1 p.Leu263Phe (c.787C>T) in the general population?

ARHGAP1 p.Leu263Phe (c.787C>T) is low-frequency (popmax 2.19%, sas) (gnomAD).

What do computational predictors say about ARHGAP1 p.Leu263Phe (c.787C>T)?

AlphaMissense predicts ambiguous (score 0.4557) — an in-silico prediction, not a clinical call.

ARHGAP1 p.Leu263Phe

c.787C>T · rs144801476 · VCV711378

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4557 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.19%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4557	ambiguous
REVEL	0.23	benign-leaning
SaProt	LLR -5.72	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.00064 · regional, not allelic
Overall
CADD	23.4	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 2.19% South Asian · 1,993/91,086 alleles

Filtering AF 2.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.08%

Overall 0.826% 13,336/1,614,122 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.19%	46
Middle Eastern	1.16%	87
European (non-Finnish)	0.853%	117
Remaining individualsnot grpmax-eligible	0.83%	120
Ashkenazi Jewishnot grpmax-eligible	0.743%	135
Admixed American	0.49%	204
African / African-American	0.139%	722
Finnishnot grpmax-eligible	0.0969%	1,032
East Asian	0.00669%	14,957

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: ARHGAP1
Protein: p.Leu263Phe
Coding: c.787C>T
MANE Select: NM_004308
dbSNP: rs144801476
Type: single nucleotide variant
Location: chr11:46680520 (GRCh38)
Gene constraint: LOEUF 0.601 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 11 PDB
Residue 263: an α-helix; the rho-gap domain

Full ARHGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP1 p.Pro52= Benign ★★ same type
ARHGAP1 p.Ala225Ser Uncertain significance ★ ⚠ same type
ARHGAP1 p.Ala26Val Uncertain significance ★ ⚠ same type
ARHGAP1 p.Ala373Thr Uncertain significance ★ ⚠ same type
ARHGAP1 p.Ala68Pro Uncertain significance ★ ⚠ same type
ARHGAP1 p.Arg234Gln Uncertain significance ★ ⚠ same type
ARHGAP1 p.Arg234Trp Uncertain significance ★ ⚠ same type
ARHGAP1 p.Arg349Trp 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/arhgap1-p-leu263phe (accessed [today's date]).

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