Is ANO6 p.Pro34= (c.102C>T) pathogenic?

ANO6 p.Pro34= (c.102C>T) is classified Benign in ANO6 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele.

ANO6 p.Pro34=

Q: How common is ANO6 p.Pro34= (c.102C>T) in the general population?

ANO6 p.Pro34= (c.102C>T) is common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.102C>T · rs7299561 · VCV257139

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -3.8, phastCons 0.001
Overall
CADD	8.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.3% African / African-American · 11,475/74,926 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 15%

Overall 0.862% 13,910/1,613,810 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.3%	7
Admixed American	1.39%	72
Remaining individualsnot grpmax-eligible	1.22%	82
Middle Eastern	1.14%	88
Ashkenazi Jewishnot grpmax-eligible	0.118%	846
South Asian	0.0911%	1,097
European (non-Finnish)	0.0536%	1,864
Finnishnot grpmax-eligible	0.025%	4,001
East Asian	0.00223%	44,872

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: ANO6
Protein: p.Pro34=
Coding: c.102C>T
MANE Select: NM_001025356
dbSNP: rs7299561
Type: single nucleotide variant
Location: chr12:45302045 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.00

Full ANO6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO6 p.Pro34Leu Uncertain significance ★ ⚠ same residue
ANO6 c.1387-1G>T Pathogenic ★★ same type
ANO6 p.Arg253Cys Uncertain significance ★★ ⚠ same type
ANO6 p.Arg253His Uncertain significance ★★ ⚠ same type
ANO6 p.Arg276Gln Uncertain significance ★★ ⚠ same type
ANO6 p.Arg399Cys Uncertain significance ★★ same type
ANO6 p.Arg635Gln Uncertain significance ★★ ⚠ same type
ANO6 p.Arg648Leu Uncertain significance ★★ ⚠ 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/ano6-p-pro34 (accessed [today's date]).

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