Is CA11 p.Ser8Gly (c.22A>G) pathogenic?

CA11 p.Ser8Gly (c.22A>G) is classified Uncertain significance in CA11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely benign (0.0646); Very rare (popmax 0.00349%, nfe).

How common is CA11 p.Ser8Gly (c.22A>G) in the general population?

CA11 p.Ser8Gly (c.22A>G) is very rare (popmax 0.00349%, nfe) (gnomAD).

What do computational predictors say about CA11 p.Ser8Gly (c.22A>G)?

AlphaMissense predicts likely benign (score 0.0646) — an in-silico prediction, not a clinical call.

CA11 p.Ser8Gly

c.22A>G · rs765428646 · VCV2516742

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0646	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 0.88, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 7,510 bp · p 1.7e-05 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00349% European (non-Finnish) · 41/1,173,212 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00234%

Overall 0.00282% 45/1,598,458 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00349%	28,615
Remaining individualsnot grpmax-eligible	0.00323%	30,916
African / African-American	0.0027%	37,076

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: CA11
Protein: p.Ser8Gly
Coding: c.22A>G
MANE Select: NM_001217
dbSNP: rs765428646
Type: single nucleotide variant
Location: chr19:48645611 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 88.39

Full CA11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA11 p.Ala139Asp Uncertain significance ★ ⚠ same type
CA11 p.Ala143Pro Uncertain significance ★ ⚠ same type
CA11 p.Ala191Thr Uncertain significance ★ ⚠ same type
CA11 p.Ala63Thr Uncertain significance ★ ⚠ same type
CA11 p.Arg209His Uncertain significance ★ ⚠ same type
CA11 p.Arg289Trp Uncertain significance ★ ⚠ same type
CA11 p.Arg318His Uncertain significance ★ ⚠ same type
CA11 p.Arg318Leu 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/ca11-p-ser8gly (accessed [today's date]).

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