Is CA10 p.Thr260Ile (c.779C>T) pathogenic?

CA10 p.Thr260Ile (c.779C>T) is classified Uncertain significance in CA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-25). AlphaMissense: likely pathogenic (0.9845); Ultra-rare (popmax 0.0163%, nfe).

How common is CA10 p.Thr260Ile (c.779C>T) in the general population?

CA10 p.Thr260Ile (c.779C>T) is ultra-rare (popmax 0.0163%, nfe) (gnomAD).

What do computational predictors say about CA10 p.Thr260Ile (c.779C>T)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

CA10 p.Thr260Ile

c.779C>T · rs781699188 · VCV3136113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0163%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic
REVEL	0.817	moderately pathogenic-leaning
SaProt	LLR -11.35	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 526 kb · p 0.0032 · regional, not allelic
Overall
CADD	32.0	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 0.0163% European (non-Finnish) · 190/1,165,318 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0124% 197/1,586,580 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0163%	6,133
Remaining individualsnot grpmax-eligible	0.00653%	15,324
African / African-American	0.00405%	24,676

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: CA10
Protein: p.Thr260Ile
Coding: c.779C>T
MANE Select: NM_020178
dbSNP: rs781699188
Type: single nucleotide variant
Location: chr17:51635865 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 85.65
Residue 260: the alpha-carbonic anhydrase domain

Full CA10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA10 p.Trp250Leu Uncertain significance ★★ ⚠ same type
CA10 p.Ala21Val Uncertain significance ★ ⚠ same type
CA10 p.Arg127Gln Uncertain significance ★ ⚠ same type
CA10 p.Arg198Gln Uncertain significance ★ ⚠ same type
CA10 p.Arg298Cys Uncertain significance ★ ⚠ same type
CA10 p.Arg65Gln Uncertain significance ★ ⚠ same type
CA10 p.Asn116Ser Uncertain significance ★ ⚠ same type
CA10 p.Asn14Ser 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/ca10-p-thr260ile (accessed [today's date]).

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