Is CA13 p.Arg247His (c.740G>A) pathogenic?

CA13 p.Arg247His (c.740G>A) is classified Uncertain significance in CA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.7576); Ultra-rare (popmax 0.0117%, amr).

How common is CA13 p.Arg247His (c.740G>A) in the general population?

CA13 p.Arg247His (c.740G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CA13 p.Arg247His (c.740G>A)?

AlphaMissense predicts likely pathogenic (score 0.7576) — an in-silico prediction, not a clinical call.

CA13 p.Arg247His

c.740G>A · rs755805228 · VCV2622711

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7576 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7576	likely pathogenic
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -9.81	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 36 kb · p 0.83 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,008 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00229% 37/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
East Asian	0.0111%	8,976
South Asian	0.00439%	22,770
African / African-American	0.004%	24,989
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	0.00136%	73,745

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: CA13
Protein: p.Arg247His
Coding: c.740G>A
MANE Select: NM_198584
dbSNP: rs755805228
Type: single nucleotide variant
Location: chr8:85281300 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.74 · 18 PDB
Residue 247: the alpha-carbonic anhydrase domain; an α-helix

Full CA13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA13 p.Ala143Pro Uncertain significance ★ ⚠ same type
CA13 p.Ala234Gly Uncertain significance ★ ⚠ same type
CA13 p.Ala240Thr Uncertain significance ★ ⚠ same type
CA13 p.Arg255Cys Uncertain significance ★ ⚠ same type
CA13 p.Arg81His Uncertain significance ★ ⚠ same type
CA13 p.Arg9Cys Uncertain significance ★ ⚠ same type
CA13 p.Asn245Asp Uncertain significance ★ ⚠ same type
CA13 p.Gln28His 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/ca13-p-arg247his (accessed [today's date]).

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