Is CA13 p.Val39Met (c.115G>A) pathogenic?

CA13 p.Val39Met (c.115G>A) is classified Uncertain significance in CA13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: ambiguous (0.3958); Very rare (popmax 0.00134%, afr).

How common is CA13 p.Val39Met (c.115G>A) in the general population?

CA13 p.Val39Met (c.115G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CA13 p.Val39Met (c.115G>A)?

AlphaMissense predicts ambiguous (score 0.3958) — an in-silico prediction, not a clinical call.

CA13 p.Val39Met

c.115G>A · rs1178610391 · VCV2294391

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3958	ambiguous
REVEL	0.247	benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.14, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 36 kb · p 0.83 · regional, not allelic
Overall
CADD	26.8	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 0.00134% African / African-American · 1/74,888 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,613,848 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,888
European (non-Finnish)	0.00119%	84,280

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.Val39Met
Coding: c.115G>A
MANE Select: NM_198584
dbSNP: rs1178610391
Type: single nucleotide variant
Location: chr8:85250817 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.74 · 18 PDB
Residue 39: the alpha-carbonic anhydrase domain; a β-strand

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.Arg247His 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

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-val39met (accessed [today's date]).

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