Is ANO8 p.Pro348Ser (c.1042C>T) pathogenic?

ANO8 p.Pro348Ser (c.1042C>T) is classified Uncertain significance in ANO8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: ambiguous (0.5138); No allele count reported in gnomAD v4.1 (AN 1,565,158).

How common is ANO8 p.Pro348Ser (c.1042C>T) in the general population?

ANO8 p.Pro348Ser (c.1042C>T) is no allele count reported in gnomAD v4.1 (AN 1,565,158) (gnomAD).

What do computational predictors say about ANO8 p.Pro348Ser (c.1042C>T)?

AlphaMissense predicts ambiguous (score 0.5138) — an in-silico prediction, not a clinical call.

ANO8 p.Pro348Ser

c.1042C>T · rs2074308894 · VCV2327195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5138 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,565,158)

Computational evidence

Protein change
AlphaMissense	0.5138	ambiguous
REVEL	0.429	indeterminate
SaProt	LLR -11.97	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 41 bp · p 0.0024 · regional, not allelic
Overall
CADD	26.3	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

No allele count reported in gnomAD v4.1 (AN 1,565,158). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ANO8
Protein: p.Pro348Ser
Coding: c.1042C>T
MANE Select: NM_020959
dbSNP: rs2074308894
Type: single nucleotide variant
Location: chr19:17330456 (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-pro348ser (accessed [today's date]).

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