Is ANO1 p.Pro116= (c.348G>A) pathogenic?

ANO1 p.Pro116= (c.348G>A) is classified Likely benign in ANO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Very rare (popmax 0.00271%, afr).

How common is ANO1 p.Pro116= (c.348G>A) in the general population?

ANO1 p.Pro116= (c.348G>A) is very rare (popmax 0.00271%, afr) (gnomAD).

ANO1 p.Pro116=

c.348G>A · VCV4681535

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.3	GERP -2.3
Overall
CADD	2.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% African / African-American · 2/73,858 alleles

Filtering AF 0.000449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000956% 15/1,568,314 alleles · very rare exomes 15/1,416,280 · genomes 0/152,034 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00495%	20,209
African / African-Americangrpmax	0.00271%	36,929
South Asian	0.00237%	42,207
Admixed American	0.00184%	54,426
European (non-Finnish)	0.000605%	165,159

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro116=
Coding: c.348G>A
MANE Select: NM_018043
Type: single nucleotide variant
Location: chr11:70087991 (GRCh38)
Gene constraint: LOEUF 0.618 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.20
Residue 116: the 'disordered' region

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-pro116 (accessed [today's date]).

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