Is CA6 p.Gln243Glu (c.727C>G) pathogenic?

CA6 p.Gln243Glu (c.727C>G) is classified Uncertain significance in CA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). AlphaMissense: likely benign (0.3312); Absent from gnomAD v4.1.

How common is CA6 p.Gln243Glu (c.727C>G) in the general population?

CA6 p.Gln243Glu (c.727C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA6 p.Gln243Glu (c.727C>G)?

AlphaMissense predicts likely benign (score 0.3312) — an in-silico prediction, not a clinical call.

CA6 p.Gln243Glu

c.727C>G · rs1356682563 · VCV2474254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3312 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3312	likely benign
REVEL	0.68	pathogenic-leaning
SaProt	LLR -10.44	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.8 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CA6
Protein: p.Gln243Glu
Coding: c.727C>G
MANE Select: NM_001215
dbSNP: rs1356682563
Type: single nucleotide variant
Location: chr1:8967814 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 1 PDB
Residue 243: the alpha-carbonic anhydrase domain; an α-helix

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-gln243glu (accessed [today's date]).

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