Is ANO8 p.Ser267Phe (c.800C>T) pathogenic?

ANO8 p.Ser267Phe (c.800C>T) is classified Uncertain significance in ANO8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely benign (0.2896); Very rare (popmax 0.000678%, nfe).

How common is ANO8 p.Ser267Phe (c.800C>T) in the general population?

ANO8 p.Ser267Phe (c.800C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about ANO8 p.Ser267Phe (c.800C>T)?

AlphaMissense predicts likely benign (score 0.2896) — an in-silico prediction, not a clinical call.

ANO8 p.Ser267Phe

c.800C>T · VCV3299106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2896	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -4.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 4,110 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	23.1	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 0.000678% European (non-Finnish) · 8/1,180,046 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,112 alleles · very rare exomes 7/1,461,886 · genomes 1/152,226 · joint denominator

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.Ser267Phe
Coding: c.800C>T
MANE Select: NM_020959
Type: single nucleotide variant
Location: chr19:17331119 (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-ser267phe (accessed [today's date]).

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