Is CA11 p.Ile255Thr (c.764T>C) pathogenic?

CA11 p.Ile255Thr (c.764T>C) is classified Uncertain significance in CA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: ambiguous (0.4606); Very rare (popmax 0.00669%, eas).

How common is CA11 p.Ile255Thr (c.764T>C) in the general population?

CA11 p.Ile255Thr (c.764T>C) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CA11 p.Ile255Thr (c.764T>C)?

AlphaMissense predicts ambiguous (score 0.4606) — an in-silico prediction, not a clinical call.

CA11 p.Ile255Thr

c.764T>C · VCV3483730

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Computational evidence

Protein change
AlphaMissense	0.4606	ambiguous
REVEL	0.485	indeterminate
SaProt	LLR -8.85	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 7,510 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	25.8	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 0.00669% East Asian · 3/44,860 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00211% 34/1,613,674 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,953
African / African-American	0.004%	24,979
European (non-Finnish)	0.00237%	42,140

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: CA11
Protein: p.Ile255Thr
Coding: c.764T>C
MANE Select: NM_001217
Type: single nucleotide variant
Location: chr19:48639336 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 88.39
Residue 255: the alpha-carbonic anhydrase domain

Full CA11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA11 p.Ala139Asp Uncertain significance ★ ⚠ same type
CA11 p.Ala143Pro Uncertain significance ★ ⚠ same type
CA11 p.Ala191Thr Uncertain significance ★ ⚠ same type
CA11 p.Ala63Thr Uncertain significance ★ ⚠ same type
CA11 p.Arg209His Uncertain significance ★ ⚠ same type
CA11 p.Arg289Trp Uncertain significance ★ ⚠ same type
CA11 p.Arg318His Uncertain significance ★ ⚠ same type
CA11 p.Arg318Leu 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/ca11-p-ile255thr (accessed [today's date]).

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