Is ANO10 p.Trp186Arg (c.556T>C) pathogenic?

ANO10 p.Trp186Arg (c.556T>C) is classified Uncertain significance in ANO10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: likely pathogenic (0.9961); Absent from gnomAD v4.1.

How common is ANO10 p.Trp186Arg (c.556T>C) in the general population?

ANO10 p.Trp186Arg (c.556T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANO10 p.Trp186Arg (c.556T>C)?

AlphaMissense predicts likely pathogenic (score 0.9961) — an in-silico prediction, not a clinical call.

ANO10 p.Trp186Arg

c.556T>C · VCV3369621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9961 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9961	likely pathogenic · top 1% in ANO10
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -13.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 239 kb · p 0.041 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANO10
Protein: p.Trp186Arg
Coding: c.556T>C
MANE Select: NM_018075
Type: single nucleotide variant
Location: chr3:43580389 (GRCh38)
Gene constraint: LOEUF 1.24 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.26 · 5 PDB
Residue 186: an α-helix

Full ANO10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO10 c.1163-9A>G Pathogenic/Likely pathogenic ★★ same type
ANO10 c.1218+1G>C Pathogenic/Likely pathogenic ★★ same type
ANO10 c.1219-1G>T Pathogenic ★★ same type
ANO10 c.139+1G>T Pathogenic/Likely pathogenic ★★ same type
ANO10 c.1797+1G>A Likely pathogenic ★★ same type
ANO10 c.472+1G>T Pathogenic/Likely pathogenic ★★ same type
ANO10 c.473-2A>G Pathogenic/Likely pathogenic ★★ same type
ANO10 c.473-2A>T Likely pathogenic ★★ 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/ano10-p-trp186arg (accessed [today's date]).

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