Is ANO7 p.Val13Ile (c.37G>A) pathogenic?

ANO7 p.Val13Ile (c.37G>A) is classified Benign in ANO7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-10). AlphaMissense: likely benign (0.0867); Common (popmax 47%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ANO7 p.Val13Ile (c.37G>A)?

AlphaMissense predicts likely benign (score 0.0867) — an in-silico prediction, not a clinical call.

ANO7 p.Val13Ile

Q: How common is ANO7 p.Val13Ile (c.37G>A) in the general population?

ANO7 p.Val13Ile (c.37G>A) is common (popmax 47%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.37G>A · rs2302054 · VCV1246662

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0867 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 47%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0867	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.29	GERP -0.097
Regional constraint	o/e 1.08	unconstrained · MANE · 34 kb · p 0.0036 · regional, not allelic
Overall
CADD	13.31	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 V67I vs ClinVar V13I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47% East Asian · 20,308/43,224 alleles

Filtering AF 46.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 46.2%

Overall 3.27% 51,768/1,584,012 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	47%	2
Admixed American	26.3%	4
South Asian	7.79%	13
Remaining individualsnot grpmax-eligible	4.64%	22
Finnishnot grpmax-eligible	3.52%	28
African / African-American	2.55%	39
Middle Eastern	0.865%	116
European (non-Finnish)	0.273%	367
Ashkenazi Jewishnot grpmax-eligible	0.173%	579

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.Val13Ile
Coding: c.37G>A
MANE Select: NM_001370694
dbSNP: rs2302054
Type: single nucleotide variant
Location: chr2:241190100 (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-val13ile (accessed [today's date]).

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