Is CA10 p.Asn116Ser (c.347A>G) pathogenic?

CA10 p.Asn116Ser (c.347A>G) is classified Uncertain significance in CA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-15). AlphaMissense: ambiguous (0.3469); Very rare (popmax 0.0011%, sas).

How common is CA10 p.Asn116Ser (c.347A>G) in the general population?

CA10 p.Asn116Ser (c.347A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CA10 p.Asn116Ser (c.347A>G)?

AlphaMissense predicts ambiguous (score 0.3469) — an in-silico prediction, not a clinical call.

CA10 p.Asn116Ser

c.347A>G · VCV3826427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3469 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.3469	ambiguous
REVEL	0.38	indeterminate
SaProt	LLR -8.53	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 526 kb · p 0.0032 · regional, not allelic
Overall
CADD	26.1	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 0.0011% South Asian · 1/91,090 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	0.000169%	590,002

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CA10
Protein: p.Asn116Ser
Coding: c.347A>G
MANE Select: NM_020178
Type: single nucleotide variant
Location: chr17:51747751 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 85.65
Residue 116: the alpha-carbonic anhydrase domain

Full CA10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA10 p.Trp250Leu Uncertain significance ★★ ⚠ same type
CA10 p.Ala21Val Uncertain significance ★ ⚠ same type
CA10 p.Arg127Gln Uncertain significance ★ ⚠ same type
CA10 p.Arg198Gln Uncertain significance ★ ⚠ same type
CA10 p.Arg298Cys Uncertain significance ★ ⚠ same type
CA10 p.Arg65Gln Uncertain significance ★ ⚠ same type
CA10 p.Asn14Ser Uncertain significance ★ ⚠ same type
CA10 p.Asn201Asp 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/ca10-p-asn116ser (accessed [today's date]).

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