Is ANO8 p.Ala342= (c.1026C>G) pathogenic?

ANO8 p.Ala342= (c.1026C>G) is classified Likely benign in ANO8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). Ultra-rare (popmax 0.0109%, afr).

How common is ANO8 p.Ala342= (c.1026C>G) in the general population?

ANO8 p.Ala342= (c.1026C>G) is ultra-rare (popmax 0.0109%, afr) (gnomAD).

ANO8 p.Ala342=

c.1026C>G · VCV3875182

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, afr)

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 -20	GERP -4.1
Overall
CADD	0.007	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% African / African-American · 8/73,318 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00277% 43/1,552,208 alleles · ultra-rare exomes 33/1,399,982 · genomes 10/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0109%	9,165
European (non-Finnish)	0.00287%	34,785
Remaining individualsnot grpmax-eligible	0.00166%	60,100
South Asian	0.0012%	83,162

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: ANO8
Protein: p.Ala342=
Coding: c.1026C>G
MANE Select: NM_020959
Type: single nucleotide variant
Location: chr19:17330472 (GRCh38)
Gene constraint: LOEUF 0.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.82

Full ANO8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO8 p.Ala1004Asp Uncertain significance ★ ⚠ same type
ANO8 p.Ala1048Pro Uncertain significance ★ ⚠ same type
ANO8 p.Ala1119Thr Uncertain significance ★ ⚠ same type
ANO8 p.Ala1119Val Uncertain significance ★ ⚠ same type
ANO8 p.Ala1167Thr Uncertain significance ★ ⚠ same type
ANO8 p.Ala1170Asp Uncertain significance ★ ⚠ same type
ANO8 p.Ala1170Thr Uncertain significance ★ ⚠ same type
ANO8 p.Ala1184Thr 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/ano8-p-ala342 (accessed [today's date]).

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