Is CA7 p.Thr110Met (c.329C>T) pathogenic?

CA7 p.Thr110Met (c.329C>T) is classified Uncertain significance in CA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.0866); Very rare (popmax 0.000254%, nfe).

How common is CA7 p.Thr110Met (c.329C>T) in the general population?

CA7 p.Thr110Met (c.329C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CA7 p.Thr110Met (c.329C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

CA7 p.Thr110Met

c.329C>T · rs1382409722 · VCV2486127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.603	indeterminate
SaProt	LLR -9.53	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.79, phastCons 0.57
Regional constraint	o/e 0.61	unconstrained · MANE · 9,007 bp · p 3.9e-13 · regional, not allelic
Overall
CADD	21.6	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 0.000254% European (non-Finnish) · 3/1,179,076 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,814 alleles · very rare

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: CA7
Protein: p.Thr110Met
Coding: c.329C>T
MANE Select: NM_005182
dbSNP: rs1382409722
Type: single nucleotide variant
Location: chr16:66850631 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 97.15 · 13 PDB
Residue 110: the alpha-carbonic anhydrase domain; a β-strand

Full CA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA7 p.Ala165Val Uncertain significance ★ ⚠ same type
CA7 p.Ala55Asp Uncertain significance ★ ⚠ same type
CA7 p.Ala55Gly Uncertain significance ★ ⚠ same type
CA7 p.Arg161Leu Uncertain significance ★ ⚠ same type
CA7 p.Arg191Trp Uncertain significance ★ ⚠ same type
CA7 p.Arg215Trp Uncertain significance ★ ⚠ same type
CA7 p.Arg256His Uncertain significance ★ ⚠ same type
CA7 p.Arg263Gln 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/ca7-p-thr110met (accessed [today's date]).

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