Is ANO1 p.Ile150Val (c.448A>G) pathogenic?

ANO1 p.Ile150Val (c.448A>G) is classified Uncertain significance in ANO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.1042); Ultra-rare (popmax 0.0134%, afr).

How common is ANO1 p.Ile150Val (c.448A>G) in the general population?

ANO1 p.Ile150Val (c.448A>G) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about ANO1 p.Ile150Val (c.448A>G)?

AlphaMissense predicts likely benign (score 0.1042) — an in-silico prediction, not a clinical call.

ANO1 p.Ile150Val

c.448A>G · rs550717562 · VCV2486585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1042 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1042	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 25 kb · p 0.27 · regional, not allelic
Overall
CADD	18.97	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 0.0134% African / African-American · 10/74,882 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000869% 14/1,610,408 alleles · ultra-rare exomes 9/1,458,292 · genomes 5/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,488
Admixed American	0.00504%	19,857
Remaining individualsnot grpmax-eligible	0.0016%	62,372

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: ANO1
Protein: p.Ile150Val
Coding: c.448A>G
MANE Select: NM_018043
dbSNP: rs550717562
Type: single nucleotide variant
Location: chr11:70103072 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.20

Full ANO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO1 p.Ser8Trp Uncertain significance ★★ ⚠ same type
ANO1 c.1504-8T>C Benign ★★ same type
ANO1 p.Ala549= Benign ★★ same type
ANO1 p.Arg81= Benign/Likely benign ★★ same type
ANO1 p.Asn617= Benign ★★ same type
ANO1 p.His426Asn Likely benign ★★ ⚠ same type
ANO1 p.His703= Likely benign ★★ same type
ANO1 p.Leu972= Benign/Likely benign ★★ 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/ano1-p-ile150val (accessed [today's date]).

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