Is ATF7 p.Ala345= (c.1035A>G) pathogenic?

ATF7 p.Ala345= (c.1035A>G) is classified Benign in ATF7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-06). Common (popmax 5.41%, afr) — too common for a highly-penetrant pathogenic allele.

ATF7 p.Ala345=

Q: How common is ATF7 p.Ala345= (c.1035A>G) in the general population?

ATF7 p.Ala345= (c.1035A>G) is common (popmax 5.41%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1035A>G · rs2229306 · VCV776711

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.41%, afr) — too common for a highly-penetrant pathogenic allele

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 -1.6	GERP -3.8
Overall
CADD	8.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.41% African / African-American · 4,057/75,048 alleles

Filtering AF 5.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.21%

Overall 0.279% 4,506/1,613,790 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.41%	18
Remaining individualsnot grpmax-eligible	0.346%	289
Admixed American	0.238%	420
Middle Eastern	0.0825%	1,212
European (non-Finnish)	0.0067%	14,935
South Asian	0.00659%	15,181

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: ATF7
Protein: p.Ala345=
Coding: c.1035A>G
MANE Select: NM_006856
dbSNP: rs2229306
Type: single nucleotide variant
Location: chr12:53524654 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.08
Residue 345: the bzip domain; the 'disordered' region; the 'essential for binding adenovirus 2 e1a' region; the 'basic motif' region

Full ATF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/atf7-p-ala345 (accessed [today's date]).

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