Is ARHGAP40 p.Ser22Thr (c.64T>A) pathogenic?

ARHGAP40 p.Ser22Thr (c.64T>A) is classified Uncertain significance in ARHGAP40 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). Absent from gnomAD v4.1.

How common is ARHGAP40 p.Ser22Thr (c.64T>A) in the general population?

ARHGAP40 p.Ser22Thr (c.64T>A) is absent from gnomAD v4.1 (gnomAD).

ARHGAP40 p.Ser22Thr

c.64T>A · VCV4642465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.039	GERP -0.13
Regional constraint	o/e 0.85	unconstrained · MANE · 48 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	14.71	PHRED · no single calibrated threshold — expert panels disagree

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: ARHGAP40
Protein: p.Ser22Thr
Coding: c.64T>A
MANE Select: NM_001164431
Type: single nucleotide variant
Location: chr20:38602006 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.96

Full ARHGAP40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP40 p.Ala153Val Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala200Asp Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala227Asp Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala233Val Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala296Val Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala385Gly Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala398Thr Uncertain significance ★ ⚠ same type
ARHGAP40 p.Ala423Thr 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/arhgap40-p-ser22thr (accessed [today's date]).

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