Is CA14 p.Arg211His (c.632G>A) pathogenic?

CA14 p.Arg211His (c.632G>A) is classified Uncertain significance in CA14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely benign (0.1818); Ultra-rare (popmax 0.0657%, mid).

How common is CA14 p.Arg211His (c.632G>A) in the general population?

CA14 p.Arg211His (c.632G>A) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

What do computational predictors say about CA14 p.Arg211His (c.632G>A)?

AlphaMissense predicts likely benign (score 0.1818) — an in-silico prediction, not a clinical call.

CA14 p.Arg211His

c.632G>A · rs142693414 · VCV2361746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1818	likely benign
REVEL	0.574	indeterminate
SaProt	LLR -13.29	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,527 bp · p 0.45 · regional, not allelic
Overall
CADD	31.0	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 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0163% 263/1,613,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
European (non-Finnish)	0.0192%	5,221
Finnishnot grpmax-eligible	0.0172%	5,820
Remaining individualsnot grpmax-eligible	0.0128%	7,810
East Asian	0.00668%	14,961
African / African-American	0.00668%	14,978
South Asian	0.00549%	18,216
Admixed American	0.00167%	59,994

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: CA14
Protein: p.Arg211His
Coding: c.632G>A
MANE Select: NM_012113
dbSNP: rs142693414
Type: single nucleotide variant
Location: chr1:150263111 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.11 · 2 PDB
Residue 211: a disulfide bond; a β-strand; the alpha-carbonic anhydrase domain

Full CA14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA14 p.Arg211Gly Uncertain significance ★ ⚠ same residue
CA14 p.Glu149= Benign ★★ same type
CA14 p.Ala158Gly Uncertain significance ★ ⚠ same type
CA14 p.Ala173Val Uncertain significance ★ ⚠ same type
CA14 p.Arg101Gln Uncertain significance ★ ⚠ same type
CA14 p.Arg232Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg264Gln Uncertain significance ★ ⚠ same type
CA14 p.Arg272His 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/ca14-p-arg211his (accessed [today's date]).

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