Is ATF6 p.Ser632= (c.1896A>G) pathogenic?

ATF6 p.Ser632= (c.1896A>G) is classified Benign in ATF6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 75.2%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with achromatopsia 7.

What condition is associated with ATF6 p.Ser632= (c.1896A>G)?

ATF6 p.Ser632= (c.1896A>G) is associated with achromatopsia 7 (ClinVar).

How is Achromatopsia inherited?

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

ATF6 p.Ser632=

Q: How common is ATF6 p.Ser632= (c.1896A>G) in the general population?

ATF6 p.Ser632= (c.1896A>G) is common (popmax 75.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1896A>G · rs9482 · VCV1167834

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 75.2%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

achromatopsia 7

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 -6.3	GERP -4.5
Overall
CADD	0.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75.2% European (non-Finnish) · 887,266/1,179,640 alleles

Filtering AF 75.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 75%

Overall 71.1% 1,147,193/1,613,144 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	80.5%	1
European (non-Finnish)grpmax	75.2%	1
Ashkenazi Jewishnot grpmax-eligible	71.9%	1
Remaining individualsnot grpmax-eligible	70.2%	1
Middle Eastern	68.8%	1
Amishnot grpmax-eligible	66.6%	2
South Asian	61.1%	2
East Asian	50.2%	2
Admixed American	44.9%	2
African / African-American	44.9%	2

Finnish 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: ATF6
Protein: p.Ser632=
Coding: c.1896A>G
MANE Select: NM_007348
dbSNP: rs9482
Type: single nucleotide variant
Location: chr1:161958537 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 56.09

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 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
ATF6 p.Ala226Glu Uncertain significance ★★ ⚠ same condition
ATF6 c.1434-3T>A Benign ★★ same condition
ATF6 p.Leu35= Benign ★★ 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-ser632 (accessed [today's date]).

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