Is ATF6 p.Pro90= (c.270T>C) pathogenic?

ATF6 p.Pro90= (c.270T>C) is classified Benign in ATF6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). Common (popmax 38.5%, amr) — too common for a highly-penetrant pathogenic allele; Associated with achromatopsia 7.

What condition is associated with ATF6 p.Pro90= (c.270T>C)?

ATF6 p.Pro90= (c.270T>C) 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.Pro90=

Q: How common is ATF6 p.Pro90= (c.270T>C) in the general population?

ATF6 p.Pro90= (c.270T>C) is common (popmax 38.5%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.270T>C · rs2271013 · VCV1164404

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 38.5%, amr) — 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 0.044	GERP 0.74, phastCons 0.7
Overall
CADD	9.688	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38.5% Admixed American · 23,087/59,908 alleles

Filtering AF 38.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.9%

Overall 8.94% 143,840/1,609,026 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	38.5%	3
East Asian	33.9%	3
Ashkenazi Jewishnot grpmax-eligible	10.4%	10
Remaining individualsnot grpmax-eligible	9.6%	10
Middle Eastern	9.18%	11
South Asian	8.57%	12
European (non-Finnish)	6.77%	15
Finnishnot grpmax-eligible	6.63%	15
African / African-American	5.76%	17
Amishnot grpmax-eligible	2.74%	36

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.Pro90=
Coding: c.270T>C
MANE Select: NM_007348
dbSNP: rs2271013
Type: single nucleotide variant
Location: chr1:161784012 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 56.09
Residue 90: the 'transcription activation' 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.Pro90His Uncertain significance ★ ⚠ same residue
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

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-pro90 (accessed [today's date]).

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