Is CA6 p.Gly102Ser (c.304G>A) pathogenic?

CA6 p.Gly102Ser (c.304G>A) is classified Uncertain significance in CA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.2656); Ultra-rare (popmax 0.02%, afr).

How common is CA6 p.Gly102Ser (c.304G>A) in the general population?

CA6 p.Gly102Ser (c.304G>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about CA6 p.Gly102Ser (c.304G>A)?

AlphaMissense predicts likely benign (score 0.2656) — an in-silico prediction, not a clinical call.

CA6 p.Gly102Ser

c.304G>A · VCV3826461

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2656 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2656	likely benign
REVEL	0.492	indeterminate
SaProt	LLR -10.03	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 7.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.8 · regional, not allelic
Overall
CADD	21.4	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 0.02% African / African-American · 15/74,976 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00217% 35/1,613,732 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,998
South Asian	0.00329%	30,351
Remaining individualsnot grpmax-eligible	0.0032%	31,246
Finnishnot grpmax-eligible	0.00156%	63,996
European (non-Finnish)	0.00119%	84,273

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: CA6
Protein: p.Gly102Ser
Coding: c.304G>A
MANE Select: NM_001215
Type: single nucleotide variant
Location: chr1:8957181 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 1 PDB
Residue 102: a disulfide bond; the alpha-carbonic anhydrase domain

Full CA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA6 p.Gly70= Benign ★★ same type
CA6 p.Ala33Val Uncertain significance ★ ⚠ same type
CA6 p.Arg255Cys Uncertain significance ★ ⚠ same type
CA6 p.Arg255Ser Uncertain significance ★ ⚠ same type
CA6 p.Arg265Gly Uncertain significance ★ ⚠ same type
CA6 p.Arg305Gly Uncertain significance ★ ⚠ same type
CA6 p.Arg96Gly Uncertain significance ★ ⚠ same type
CA6 p.Asn280Tyr 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/ca6-p-gly102ser (accessed [today's date]).

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