Is CA5B p.Met277Val (c.829A>G) pathogenic?

CA5B p.Met277Val (c.829A>G) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). AlphaMissense: likely pathogenic (0.8478); Absent from gnomAD v4.1.

How common is CA5B p.Met277Val (c.829A>G) in the general population?

CA5B p.Met277Val (c.829A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA5B p.Met277Val (c.829A>G)?

AlphaMissense predicts likely pathogenic (score 0.8478) — an in-silico prediction, not a clinical call.

CA5B p.Met277Val

c.829A>G · VCV3994228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8478	likely pathogenic
REVEL	0.61	indeterminate
SaProt	LLR -9.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 18 kb · p 0.53 · regional, not allelic
Overall
CADD	24.6	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.Met277Val
Coding: c.829A>G
MANE Select: NM_007220
Type: single nucleotide variant
Location: chrX:15782539 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 277: 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-met277val (accessed [today's date]).

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