Is ANO7 p.Phe555Ile (c.1663T>A) pathogenic?

ANO7 p.Phe555Ile (c.1663T>A) is classified Uncertain significance in ANO7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-07). AlphaMissense: ambiguous (0.4811); Ultra-rare (popmax 0.0919%, afr).

How common is ANO7 p.Phe555Ile (c.1663T>A) in the general population?

ANO7 p.Phe555Ile (c.1663T>A) is ultra-rare (popmax 0.0919%, afr) (gnomAD).

What do computational predictors say about ANO7 p.Phe555Ile (c.1663T>A)?

AlphaMissense predicts ambiguous (score 0.4811) — an in-silico prediction, not a clinical call.

ANO7 p.Phe555Ile

c.1663T>A · rs138179358 · VCV2287637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4811 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0919%, afr)

Computational evidence

Protein change
AlphaMissense	0.4811	ambiguous
REVEL	0.386	indeterminate
SaProt	LLR -9.51	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 2.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.0036 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F609I vs ClinVar F555I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0919% African / African-American · 69/75,058 alleles

Filtering AF 0.0744% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.00459% 74/1,613,810 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0919%	1,088
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.00167%	60,026

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: ANO7
Protein: p.Phe555Ile
Coding: c.1663T>A
MANE Select: NM_001370694
dbSNP: rs138179358
Type: single nucleotide variant
Location: chr2:241212195 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.56

Full ANO7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO7 c.1077+10G>A Benign ★★ same type
ANO7 c.1077+73C>A Benign ★★ same type
ANO7 c.108+183T>G Benign ★★ same type
ANO7 c.1359+129A>G Benign ★★ same type
ANO7 c.1359+23G>A Benign ★★ same type
ANO7 c.1459-5G>A Benign ★★ same type
ANO7 c.1561+106T>C Benign ★★ same type
ANO7 c.1561+64C>T 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/ano7-p-phe555ile (accessed [today's date]).

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