Is CA5B p.Asp226His (c.676G>C) pathogenic?

CA5B p.Asp226His (c.676G>C) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: ambiguous (0.4635); Absent from gnomAD v4.1.

How common is CA5B p.Asp226His (c.676G>C) in the general population?

CA5B p.Asp226His (c.676G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA5B p.Asp226His (c.676G>C)?

AlphaMissense predicts ambiguous (score 0.4635) — an in-silico prediction, not a clinical call.

CA5B p.Asp226His

c.676G>C · VCV3826458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4635 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4635	ambiguous
REVEL	0.597	indeterminate
SaProt	LLR -8.20	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 0.95, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 18 kb · p 0.53 · 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

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: CA5B
Protein: p.Asp226His
Coding: c.676G>C
MANE Select: NM_007220
Type: single nucleotide variant
Location: chrX:15776771 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 226: the alpha-carbonic anhydrase domain

Full CA5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA5B p.Ala135Pro Uncertain significance ★ ⚠ same type
CA5B p.Ala138Val Uncertain significance ★ ⚠ same type
CA5B p.Ala170Glu Uncertain significance ★ ⚠ same type
CA5B p.Ala47Val Uncertain significance ★ ⚠ same type
CA5B p.Arg282Cys Uncertain significance ★ ⚠ same type
CA5B p.Arg282His Uncertain significance ★ ⚠ same type
CA5B p.Arg290Leu Uncertain significance ★ ⚠ same type
CA5B p.Arg293His 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/ca5b-p-asp226his (accessed [today's date]).

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