Is ARHGAP23 p.Asn2Ser (c.5A>G) pathogenic?

ARHGAP23 p.Asn2Ser (c.5A>G) is classified Uncertain significance in ARHGAP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: ambiguous (0.5214); Very rare (popmax 0.0074%, amr).

How common is ARHGAP23 p.Asn2Ser (c.5A>G) in the general population?

ARHGAP23 p.Asn2Ser (c.5A>G) is very rare (popmax 0.0074%, amr) (gnomAD).

What do computational predictors say about ARHGAP23 p.Asn2Ser (c.5A>G)?

AlphaMissense predicts ambiguous (score 0.5214) — an in-silico prediction, not a clinical call.

ARHGAP23 p.Asn2Ser

c.5A>G · VCV3422141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5214 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0074%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5214	ambiguous
REVEL	0.049	moderately benign-leaning
SaProt	LLR -5.18	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 10	GERP 1.1, phastCons 1
Overall
CADD	24.1	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 0.0074% Admixed American · 3/40,562 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000277% 4/1,446,162 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0074%	13,521
Remaining individualsnot grpmax-eligible	0.00181%	55,214

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: ARHGAP23
Protein: p.Asn2Ser
Coding: c.5A>G
MANE Select: NM_001199417
Type: single nucleotide variant
Location: chr17:38428490 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.82

Full ARHGAP23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP23 p.Ala1010Thr Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1010Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1153Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1222Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1324Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1340Thr Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1363Val Uncertain significance ★ ⚠ same type
ARHGAP23 p.Ala1457Val 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/arhgap23-p-asn2ser (accessed [today's date]).

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