Is CA10 p.Thr167Met (c.500C>T) pathogenic?

CA10 p.Thr167Met (c.500C>T) is classified Uncertain significance in CA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely benign (0.0977); Very rare (popmax 0.0044%, sas).

How common is CA10 p.Thr167Met (c.500C>T) in the general population?

CA10 p.Thr167Met (c.500C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

What do computational predictors say about CA10 p.Thr167Met (c.500C>T)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

CA10 p.Thr167Met

c.500C>T · rs777074047 · VCV2544630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 526 kb · p 0.0032 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0044% South Asian · 4/91,002 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00226%

Overall 0.00304% 49/1,610,366 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0044%	22,750
African / African-American	0.00401%	24,939
European (non-Finnish)	0.0034%	29,419
East Asian	0.00223%	44,866
Admixed American	0.00167%	59,992

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.Thr167Met
Coding: c.500C>T
MANE Select: NM_020178
dbSNP: rs777074047
Type: single nucleotide variant
Location: chr17:51653702 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 85.65
Residue 167: 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-thr167met (accessed [today's date]).

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