Is CA13 p.Arg255Cys (c.763C>T) pathogenic?

CA13 p.Arg255Cys (c.763C>T) is classified Uncertain significance in CA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.7415); Ultra-rare (popmax 0.0245%, eas).

How common is CA13 p.Arg255Cys (c.763C>T) in the general population?

CA13 p.Arg255Cys (c.763C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about CA13 p.Arg255Cys (c.763C>T)?

AlphaMissense predicts likely pathogenic (score 0.7415) — an in-silico prediction, not a clinical call.

CA13 p.Arg255Cys

c.763C>T · VCV3483741

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7415 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7415	likely pathogenic
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -10.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 36 kb · p 0.83 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,876 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00155% 25/1,613,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,080
Admixed American	0.00167%	59,986
European (non-Finnish)	0.0011%	90,761

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: CA13
Protein: p.Arg255Cys
Coding: c.763C>T
MANE Select: NM_198584
Type: single nucleotide variant
Location: chr8:85281323 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.74 · 18 PDB
Residue 255: the alpha-carbonic anhydrase domain; an α-helix

Full CA13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA13 p.Ala143Pro Uncertain significance ★ ⚠ same type
CA13 p.Ala234Gly Uncertain significance ★ ⚠ same type
CA13 p.Ala240Thr Uncertain significance ★ ⚠ same type
CA13 p.Arg247His Uncertain significance ★ ⚠ same type
CA13 p.Arg81His Uncertain significance ★ ⚠ same type
CA13 p.Arg9Cys Uncertain significance ★ ⚠ same type
CA13 p.Asn245Asp Uncertain significance ★ ⚠ same type
CA13 p.Gln28His 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/ca13-p-arg255cys (accessed [today's date]).

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