Is CA14 p.Glu149= (c.447G>A) pathogenic?

CA14 p.Glu149= (c.447G>A) is classified Benign in CA14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-14). Common (popmax 8.03%, afr) — too common for a highly-penetrant pathogenic allele.

CA14 p.Glu149=

Q: How common is CA14 p.Glu149= (c.447G>A) in the general population?

CA14 p.Glu149= (c.447G>A) is common (popmax 8.03%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.447G>A · rs74126633 · VCV775598

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 8.03%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.47	GERP -2.9, phastCons 0.98
Overall
CADD	4.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.03% African / African-American · 6,014/74,938 alleles

Filtering AF 7.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.79%

Overall 0.428% 6,905/1,614,036 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.03%	12
Admixed American	0.626%	160
Remaining individualsnot grpmax-eligible	0.522%	192
Middle Eastern	0.313%	319
South Asian	0.0176%	5,692
European (non-Finnish)	0.013%	7,712
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Glu149=
Coding: c.447G>A
MANE Select: NM_012113
dbSNP: rs74126633
Type: single nucleotide variant
Location: chr1:150262572 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.11 · 2 PDB
Residue 149: a disulfide bond; an α-helix; the alpha-carbonic anhydrase domain

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

Similar variants

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
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-glu149 (accessed [today's date]).

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