Is CA7 p.Ala165Val (c.494C>T) pathogenic?

CA7 p.Ala165Val (c.494C>T) is classified Uncertain significance in CA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-11). AlphaMissense: likely benign (0.1977); Very rare (popmax 0.00667%, afr).

How common is CA7 p.Ala165Val (c.494C>T) in the general population?

CA7 p.Ala165Val (c.494C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about CA7 p.Ala165Val (c.494C>T)?

AlphaMissense predicts likely benign (score 0.1977) — an in-silico prediction, not a clinical call.

CA7 p.Ala165Val

c.494C>T · VCV4217549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1977	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -5.55	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 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 9,007 bp · p 3.9e-13 · regional, not allelic
Overall
CADD	23.0	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 0.00667% African / African-American · 5/74,924 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00415% 67/1,613,860 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,985
European (non-Finnish)	0.00483%	20,700
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00167%	59,974
South Asian	0.0011%	91,062

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.Ala165Val
Coding: c.494C>T
MANE Select: NM_005182
Type: single nucleotide variant
Location: chr16:66851704 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 97.15 · 13 PDB
Residue 165: the alpha-carbonic anhydrase domain; an α-helix

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

Similar variants

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
CA7 p.Arg91His 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-ala165val (accessed [today's date]).

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