Is CA14 p.Arg272His (c.815G>A) pathogenic?

CA14 p.Arg272His (c.815G>A) is classified Uncertain significance in CA14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: ambiguous (0.5329); Ultra-rare (popmax 0.0165%, mid).

How common is CA14 p.Arg272His (c.815G>A) in the general population?

CA14 p.Arg272His (c.815G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CA14 p.Arg272His (c.815G>A)?

AlphaMissense predicts ambiguous (score 0.5329) — an in-silico prediction, not a clinical call.

CA14 p.Arg272His

c.815G>A · rs369770952 · VCV3136123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5329 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5329	ambiguous
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -9.18	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,527 bp · p 0.45 · regional, not allelic
Overall
CADD	33.0	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 0.0165% Middle Eastern · 1/6,066 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00186% 30/1,614,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,066
African / African-American	0.00935%	10,700
Admixed American	0.00333%	30,003
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00144%	69,415
South Asian	0.0011%	91,078

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.Arg272His
Coding: c.815G>A
MANE Select: NM_012113
dbSNP: rs369770952
Type: single nucleotide variant
Location: chr1:150263393 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.11 · 2 PDB
Residue 272: the alpha-carbonic anhydrase domain

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

Similar variants

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.Arg211Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg211His Uncertain significance ★ ⚠ same type
CA14 p.Arg232Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg264Gln 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-arg272his (accessed [today's date]).

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