Is CA7 p.Arg256His (c.767G>A) pathogenic?

CA7 p.Arg256His (c.767G>A) is classified Uncertain significance in CA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: likely pathogenic (0.87); Very rare (popmax 0.00666%, amr).

How common is CA7 p.Arg256His (c.767G>A) in the general population?

CA7 p.Arg256His (c.767G>A) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CA7 p.Arg256His (c.767G>A)?

AlphaMissense predicts likely pathogenic (score 0.87) — an in-silico prediction, not a clinical call.

CA7 p.Arg256His

c.767G>A · rs751864019 · VCV2290422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.87 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.87	likely pathogenic
REVEL	0.899	moderately pathogenic-leaning
SaProt	LLR -10.54	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 1.9, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 9,007 bp · p 3.9e-13 · regional, not allelic
Overall
CADD	33.0	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 0.00666% Admixed American · 4/60,018 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000684% 10/1,461,828 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,004
European (non-Finnish)	0.000508%	196,671

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.Arg256His
Coding: c.767G>A
MANE Select: NM_005182
dbSNP: rs751864019
Type: single nucleotide variant
Location: chr16:66853470 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 97.15 · 13 PDB
Residue 256: 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.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.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-arg256his (accessed [today's date]).

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