Is ARHGAP30 p.Pro450Ser (c.1348C>T) pathogenic?

ARHGAP30 p.Pro450Ser (c.1348C>T) is classified Uncertain significance in ARHGAP30 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: ambiguous (0.5344); Very rare (popmax 0.00133%, afr).

How common is ARHGAP30 p.Pro450Ser (c.1348C>T) in the general population?

ARHGAP30 p.Pro450Ser (c.1348C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ARHGAP30 p.Pro450Ser (c.1348C>T)?

AlphaMissense predicts ambiguous (score 0.5344) — an in-silico prediction, not a clinical call.

ARHGAP30 p.Pro450Ser

c.1348C>T · VCV4919092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5344 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5344	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.26	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 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 4,961 bp · p 0.11 · regional, not allelic
Overall
CADD	26.6	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 0.00133% African / African-American · 1/75,070 alleles

Overall 0.00131% 2/152,384 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00157%	63,800
African / African-Americangrpmax	0.00133%	75,070

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARHGAP30
Protein: p.Pro450Ser
Coding: c.1348C>T
MANE Select: NM_001025598
Type: single nucleotide variant
Location: chr1:161051386 (GRCh38)
Gene constraint: LOEUF 0.429 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.85

Full ARHGAP30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP30 c.1420+1G>C Uncertain significance ★ same type
ARHGAP30 p.Ala1041Val Uncertain significance ★ ⚠ same type
ARHGAP30 p.Ala13Thr Uncertain significance ★ ⚠ same type
ARHGAP30 p.Ala237Thr Uncertain significance ★ ⚠ same type
ARHGAP30 p.Ala479Pro Uncertain significance ★ ⚠ same type
ARHGAP30 p.Ala482Thr Uncertain significance ★ ⚠ same type
ARHGAP30 p.Ala539Thr Uncertain significance ★ ⚠ same type
ARHGAP30 p.Ala594Thr 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/arhgap30-p-pro450ser (accessed [today's date]).

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