Is CA14 p.Asp49Asn (c.145G>A) pathogenic?

CA14 p.Asp49Asn (c.145G>A) is classified Likely benign in CA14 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely benign (0.0606); Ultra-rare (popmax 0.0165%, mid).

How common is CA14 p.Asp49Asn (c.145G>A) in the general population?

CA14 p.Asp49Asn (c.145G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CA14 p.Asp49Asn (c.145G>A)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

CA14 p.Asp49Asn

c.145G>A · rs1651030117 · VCV2604441

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -0.65, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 6,527 bp · p 0.45 · regional, not allelic
Overall
CADD	13.61	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 · 1/6,062 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000821% 12/1,461,864 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.0022%	45,542
African / African-American	0.00133%	75,028
European (non-Finnish)	0.000678%	147,500

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.Asp49Asn
Coding: c.145G>A
MANE Select: NM_012113
dbSNP: rs1651030117
Type: single nucleotide variant
Location: chr1:150261527 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.11 · 2 PDB
Residue 49: a disulfide bond; 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-asp49asn (accessed [today's date]).

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