Is ARHGAP29 p.Ser552Pro (c.1654T>C) pathogenic?

ARHGAP29 p.Ser552Pro (c.1654T>C) is classified Pathogenic in ARHGAP29 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely pathogenic (0.7144); Absent from gnomAD v4.1; Associated with ARHGAP29-related disorder.

What condition is associated with ARHGAP29 p.Ser552Pro (c.1654T>C)?

ARHGAP29 p.Ser552Pro (c.1654T>C) is associated with ARHGAP29-related disorder (ClinVar).

How common is ARHGAP29 p.Ser552Pro (c.1654T>C) in the general population?

ARHGAP29 p.Ser552Pro (c.1654T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP29 p.Ser552Pro (c.1654T>C)?

AlphaMissense predicts likely pathogenic (score 0.7144) — an in-silico prediction, not a clinical call.

ARHGAP29 p.Ser552Pro

c.1654T>C · VCV4901587

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7144 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARHGAP29-related disorder

Computational evidence

Protein change
AlphaMissense	0.7144	likely pathogenic ✓ concordant with ClinVar
REVEL	0.26	benign-leaning
SaProt	LLR -8.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 45 kb · p 0.027 · regional, not allelic
Overall
CADD	26.7	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

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.Ser552Pro
Coding: c.1654T>C
MANE Select: NM_004815
Type: single nucleotide variant
Location: chr1:94188864 (GRCh38)
Gene constraint: LOEUF 0.448 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.41
Residue 552: a modified residue (phosphoserine); a UniProt-annotated variant site (in a breast cancer sample; somatic mutation); the 'disordered' region

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

Disease context

ARHGAP29-related disorder

Similar variants

ARHGAP29 p.Ser552Ala Uncertain significance ★ ⚠ same residue
ARHGAP29 c.1682-12A>G Likely pathogenic ★ same condition
ARHGAP29 c.2481-1G>A Conflicting classifications of pathogenicity ★ ⚠ same condition
ARHGAP29 c.2796+5G>C Uncertain significance ★ same condition
ARHGAP29 p.Ile410Ser Uncertain significance ★ ⚠ same condition
ARHGAP29 p.Arg1024Gly Uncertain significance ⚠ same condition
ARHGAP29 p.Arg415Gln Uncertain significance ⚠ same condition
ARHGAP29 c.1144-9T>A Likely 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/arhgap29-p-ser552pro (accessed [today's date]).

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