Is CA5B p.Leu83Val (c.247C>G) pathogenic?

CA5B p.Leu83Val (c.247C>G) is classified Uncertain significance in CA5B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely benign (0.1917); Very rare (popmax 0.00158%, nfe).

How common is CA5B p.Leu83Val (c.247C>G) in the general population?

CA5B p.Leu83Val (c.247C>G) is very rare (popmax 0.00158%, nfe) (gnomAD).

What do computational predictors say about CA5B p.Leu83Val (c.247C>G)?

AlphaMissense predicts likely benign (score 0.1917) — an in-silico prediction, not a clinical call.

CA5B p.Leu83Val

c.247C>G · rs1379030882 · VCV2329764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00158%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1917	likely benign
REVEL	0.509	indeterminate
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 152 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	21.5	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 0.00158% European (non-Finnish) · 14/886,323 alleles

Filtering AF 0.000916% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00117% 14/1,196,499 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: CA5B
Protein: p.Leu83Val
Coding: c.247C>G
MANE Select: NM_007220
dbSNP: rs1379030882
Type: single nucleotide variant
Location: chrX:15764682 (GRCh38)
Structure: AlphaFold pLDDT 83.33
Residue 83: the alpha-carbonic anhydrase domain

Full CA5B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA5B p.Leu83Arg Uncertain significance ★ ⚠ same residue
CA5B p.Ala135Pro Uncertain significance ★ ⚠ same type
CA5B p.Ala138Val Uncertain significance ★ ⚠ same type
CA5B p.Ala170Glu Uncertain significance ★ ⚠ same type
CA5B p.Ala47Val Uncertain significance ★ ⚠ same type
CA5B p.Arg282Cys Uncertain significance ★ ⚠ same type
CA5B p.Arg282His Uncertain significance ★ ⚠ same type
CA5B p.Arg290Leu 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/ca5b-p-leu83val (accessed [today's date]).

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