Is ANO5 p.Asp69fs (c.206_207del) pathogenic?

ANO5 p.Asp69fs (c.206207del) is classified Pathogenic/Likely pathogenic in ANO5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-19). Very rare (popmax 0.000255%, nfe).

How common is ANO5 p.Asp69fs (c.206_207del) in the general population?

ANO5 p.Asp69fs (c.206_207del) is very rare (popmax 0.000255%, nfe) (gnomAD).

ANO5 p.Asp69fs

c.206_207del · rs1254796261 · VCV1013307

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000255% European (non-Finnish) · 3/1,178,542 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,611,540 alleles · very rare

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: ANO5
Protein: p.Asp69fs
Coding: c.206_207del
MANE Select: NM_213599
dbSNP: rs1254796261
Type: Deletion
Location: chr11:22221122 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.22

Full ANO5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANO5 p.Lys102fs Pathogenic ★★★ same type
ANO5 p.Phe835del Likely pathogenic ★★★ same type
ANO5 c.139-1del Uncertain significance ★★★ same type
ANO5 c.2236-21_2236-17del Likely benign ★★★ same type
ANO5 c.364-8del Benign ★★★ same type
ANO5 c.1631-12_1631-2del Pathogenic/Likely pathogenic ★★ same type
ANO5 p.Ala144fs Pathogenic ★★ same type
ANO5 p.Ala724_His725insTer Pathogenic ★★ 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/ano5-p-asp69fs (accessed [today's date]).

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