Is CA3 p.Asn62Ser (c.185A>G) pathogenic?

CA3 p.Asn62Ser (c.185A>G) is classified Uncertain significance in CA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.1568); Ultra-rare (popmax 0.0165%, mid).

How common is CA3 p.Asn62Ser (c.185A>G) in the general population?

CA3 p.Asn62Ser (c.185A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CA3 p.Asn62Ser (c.185A>G)?

AlphaMissense predicts likely benign (score 0.1568) — an in-silico prediction, not a clinical call.

CA3 p.Asn62Ser

c.185A>G · rs542149751 · VCV2354637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1568 · 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	0.1568	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -7.85	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 6.2	GERP 0.64, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 9,240 bp · p 0.065 · regional, not allelic
Overall
CADD	19.87	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 · 1/6,044 alleles

Filtering AF 0.00239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00266% 43/1,613,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,044
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00322%	31,052
Remaining individualsnot grpmax-eligible	0.0016%	62,502
African / African-American	0.00133%	75,048
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: CA3
Protein: p.Asn62Ser
Coding: c.185A>G
MANE Select: NM_005181
dbSNP: rs542149751
Type: single nucleotide variant
Location: chr8:85439862 (GRCh38)
Gene constraint: LOEUF 1.215 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.99 · 5 PDB
Residue 62: the alpha-carbonic anhydrase domain

Full CA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA3 p.Ala115Glu Uncertain significance ★ ⚠ same type
CA3 p.Ala232Thr Uncertain significance ★ ⚠ same type
CA3 p.Arg188Gln Uncertain significance ★ ⚠ same type
CA3 p.Asp179Gly Uncertain significance ★ ⚠ same type
CA3 p.Glu26Gln Uncertain significance ★ ⚠ same type
CA3 p.Gly82Cys Uncertain significance ★ ⚠ same type
CA3 p.Gly82Ser Uncertain significance ★ ⚠ same type
CA3 p.His10Tyr 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/ca3-p-asn62ser (accessed [today's date]).

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