Is CA9 p.Ser71Pro (c.211T>C) pathogenic?

CA9 p.Ser71Pro (c.211T>C) is classified Likely benign in CA9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: likely benign (0.0502); Ultra-rare (popmax 0.0134%, eas).

How common is CA9 p.Ser71Pro (c.211T>C) in the general population?

CA9 p.Ser71Pro (c.211T>C) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CA9 p.Ser71Pro (c.211T>C)?

AlphaMissense predicts likely benign (score 0.0502) — an in-silico prediction, not a clinical call.

CA9 p.Ser71Pro

c.211T>C · rs371183397 · VCV2518218

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0502 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0502	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -4.16	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 0.32	GERP -0.98, phastCons 0.94
Regional constraint	o/e 0.99	unconstrained · MANE · 7,062 bp · p 0.76 · regional, not allelic
Overall
CADD	1.526	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 0.0134% East Asian · 6/44,874 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00266% 43/1,614,024 alleles · ultra-rare exomes 37/1,461,812 · genomes 6/152,212 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0496%	2,016
East Asiangrpmax	0.0134%	7,479
Admixed American	0.005%	20,003
South Asian	0.0011%	91,068
European (non-Finnish)	0.000169%	589,977

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CA9
Protein: p.Ser71Pro
Coding: c.211T>C
MANE Select: NM_001216
dbSNP: rs371183397
Type: single nucleotide variant
Location: chr9:35674170 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.13 · 32 PDB
Residue 71: the 'proteoglycan-like (pg)' region; the 'disordered' region

Full CA9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA9 p.Pro114= Benign ★★ same type
CA9 p.Ala155Thr Uncertain significance ★ ⚠ same type
CA9 p.Ala176Val Uncertain significance ★ ⚠ same type
CA9 p.Ala232Val Uncertain significance ★ ⚠ same type
CA9 p.Ala300Ser Uncertain significance ★ ⚠ same type
CA9 p.Ala353Thr Uncertain significance ★ ⚠ same type
CA9 p.Ala377Glu Uncertain significance ★ ⚠ same type
CA9 p.Ala425Ser 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/ca9-p-ser71pro (accessed [today's date]).

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