Is ARHGAP31 p.Thr1404Arg (c.4211C>G) pathogenic?

ARHGAP31 p.Thr1404Arg (c.4211C>G) is classified Likely benign in ARHGAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). AlphaMissense: ambiguous (0.4089); Ultra-rare (popmax 0.0824%, eas).

How common is ARHGAP31 p.Thr1404Arg (c.4211C>G) in the general population?

ARHGAP31 p.Thr1404Arg (c.4211C>G) is ultra-rare (popmax 0.0824%, eas) (gnomAD).

What do computational predictors say about ARHGAP31 p.Thr1404Arg (c.4211C>G)?

AlphaMissense predicts ambiguous (score 0.4089) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Thr1404Arg

c.4211C>G · rs552532282 · VCV2717271

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4089 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4089	ambiguous
REVEL	0.2	benign-leaning
SaProt	LLR -6.15	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 2.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	25.3	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 0.0824% East Asian · 37/44,886 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00297% 48/1,614,210 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0824%	1,213
Remaining individualsnot grpmax-eligible	0.008%	12,500
South Asian	0.00549%	18,218
European (non-Finnish)	8.47e-05%	1,180,044

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: ARHGAP31
Protein: p.Thr1404Arg
Coding: c.4211C>G
MANE Select: NM_020754
dbSNP: rs552532282
Type: single nucleotide variant
Location: chr3:119416140 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32

Full ARHGAP31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP31 p.Ala18Val Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Ala634Asp Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg1377Ser Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg199Gln Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg256Cys Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg426Gly Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg478His Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg510Ser 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/arhgap31-p-thr1404arg (accessed [today's date]).

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