Is ARHGAP29 p.Ser736Pro (c.2206T>C) pathogenic?

ARHGAP29 p.Ser736Pro (c.2206T>C) is classified Uncertain significance in ARHGAP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.0952); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ARHGAP29 p.Ser736Pro (c.2206T>C)?

ARHGAP29 p.Ser736Pro (c.2206T>C) is associated with Inborn genetic diseases (ClinVar).

How common is ARHGAP29 p.Ser736Pro (c.2206T>C) in the general population?

ARHGAP29 p.Ser736Pro (c.2206T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP29 p.Ser736Pro (c.2206T>C)?

AlphaMissense predicts likely benign (score 0.0952) — an in-silico prediction, not a clinical call.

ARHGAP29 p.Ser736Pro

c.2206T>C · rs2524238091 · VCV2300541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0952 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0952	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -4.30	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 1.2	GERP -0.83, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.22 · regional, not allelic
Overall
CADD	13.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP29
Protein: p.Ser736Pro
Coding: c.2206T>C
MANE Select: NM_004815
dbSNP: rs2524238091
Type: single nucleotide variant
Location: chr1:94184192 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.41
Residue 736: the rho-gap domain

Full ARHGAP29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARHGAP29 p.Gln19His Uncertain significance ★★ ⚠ same condition
ARHGAP29 p.Met318Val Uncertain significance ★★ ⚠ same condition
ARHGAP29 p.Trp533Arg Uncertain significance ★★ ⚠ same condition
ARHGAP29 p.Ala110Glu Uncertain significance ★ ⚠ same condition
ARHGAP29 p.Ala1212Glu Uncertain significance ★ ⚠ same condition
ARHGAP29 p.Ala140Val Uncertain significance ★ ⚠ same condition
ARHGAP29 p.Ala812Thr Uncertain significance ★ ⚠ same condition
ARHGAP29 p.Ala959Val Uncertain significance ★ ⚠ 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/arhgap29-p-ser736pro (accessed [today's date]).

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