Is ARHGAP31 p.Pro274Ser (c.820C>T) pathogenic?

ARHGAP31 p.Pro274Ser (c.820C>T) is classified Benign/Likely benign in ARHGAP31 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-01). AlphaMissense: likely pathogenic (0.8811); Rare (popmax 0.695%, nfe); Associated with Adams-Oliver syndrome 1.

What condition is associated with ARHGAP31 p.Pro274Ser (c.820C>T)?

ARHGAP31 p.Pro274Ser (c.820C>T) is associated with Adams-Oliver syndrome 1 (ClinVar).

How common is ARHGAP31 p.Pro274Ser (c.820C>T) in the general population?

ARHGAP31 p.Pro274Ser (c.820C>T) is rare (popmax 0.695%, nfe) (gnomAD).

What do computational predictors say about ARHGAP31 p.Pro274Ser (c.820C>T)?

AlphaMissense predicts likely pathogenic (score 0.8811) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Pro274Ser

c.820C>T · rs139600783 · VCV198582

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

AlphaMissense

likely pathogenic

0.8811 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.695%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Adams-Oliver syndrome 1

Computational evidence

Protein change
AlphaMissense	0.8811	likely pathogenic
REVEL	0.102	moderately benign-leaning
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · 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 0.695% European (non-Finnish) · 8,205/1,180,018 alleles

Filtering AF 0.683% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.678%

Overall 0.562% 9,066/1,614,176 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.695%	144
Finnishnot grpmax-eligible	0.609%	164
Ashkenazi Jewishnot grpmax-eligible	0.459%	218
Remaining individualsnot grpmax-eligible	0.363%	275
African / African-American	0.0919%	1,088
Admixed American	0.0633%	1,580
South Asian	0.0011%	91,086

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.Pro274Ser
Coding: c.820C>T
MANE Select: NM_020754
dbSNP: rs139600783
Type: single nucleotide variant
Location: chr3:119390922 (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

Disease context

Adams-Oliver syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARHGAP31 p.Arg426Gly Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Gln1233Leu Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.His48Tyr Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Lys449Glu Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Trp304Ter Uncertain significance ★★ same condition
ARHGAP31 c.100+77A>T Benign ★★ same condition
ARHGAP31 c.1070-92G>C Benign ★★ same condition
ARHGAP31 c.1926+11T>C Benign ★★ same condition

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-pro274ser (accessed [today's date]).

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