Is ATF6 p.Trp486Ter (c.1457G>A) pathogenic?

ATF6 p.Trp486Ter (c.1457G>A) is classified Pathogenic in ATF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-17). Very rare (popmax 0.00017%, nfe).

How common is ATF6 p.Trp486Ter (c.1457G>A) in the general population?

ATF6 p.Trp486Ter (c.1457G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

ATF6 p.Trp486Ter

c.1457G>A · rs2525344279 · VCV2718613

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Overall
CADD	42.0	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 0.00017% European (non-Finnish) · 2/1,177,270 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,458,402 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.Trp486Ter
Coding: c.1457G>A
MANE Select: NM_007348
dbSNP: rs2525344279
Type: single nucleotide variant
Location: chr1:161853247 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 56.09
Residue 486: the 'interaction with thbs4' region

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

Similar variants

ATF6 c.1533+1G>C Pathogenic ★★ same type
ATF6 c.160-1G>A Likely pathogenic ★★ same type
ATF6 c.484+1G>A Likely pathogenic ★★ same type
ATF6 c.484+1G>T Likely pathogenic ★★ same type
ATF6 c.82+5G>T Pathogenic ★★ same type
ATF6 p.Arg324Cys Pathogenic ★★ same type
ATF6 p.Arg376Ter Pathogenic ★★ same type
ATF6 p.Gln237Ter 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/atf6-p-trp486ter (accessed [today's date]).

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