Is ATF6 p.Pro118fs (c.353del) pathogenic?

ATF6 p.Pro118fs (c.353del) is classified Pathogenic in ATF6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-21). Very rare (popmax 8.54e-05%, nfe); Associated with achromatopsia 7.

What condition is associated with ATF6 p.Pro118fs (c.353del)?

ATF6 p.Pro118fs (c.353del) is associated with achromatopsia 7 (ClinVar).

How common is ATF6 p.Pro118fs (c.353del) in the general population?

ATF6 p.Pro118fs (c.353del) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

How is Achromatopsia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ATF6 p.Pro118fs

c.353del · rs797045171 · VCV209097

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Conditions

achromatopsia 7

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 4 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP 0.96

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,171,366 alleles

Overall 6.89e-05% 1/1,451,540 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: ATF6
Protein: p.Pro118fs
Coding: c.353del
MANE Select: NM_007348
dbSNP: rs797045171
Type: Deletion
Location: chr1:161784094 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 56.09
Residue 118: the 'transcription activation' region; the 'disordered' region

Full ATF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

achromatopsia 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Achromatopsia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

ATF6 p.Gly261fs Likely pathogenic ★ same condition
ATF6 p.Ile171fs Pathogenic ★ same condition
ATF6 p.Leu595fs Likely pathogenic same condition
ATF6 c.1533+1G>C Pathogenic ★★ same condition
ATF6 c.82+5G>T Pathogenic ★★ same condition
ATF6 p.Arg324Cys Pathogenic ★★ same condition
ATF6 p.Arg376Ter Pathogenic ★★ same condition
ATF6 p.Gln237Ter Pathogenic ★★ same condition

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/atf6-p-pro118fs (accessed [today's date]).

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