Is ATF4 p.Glu3Lys (c.7G>A) pathogenic?

ATF4 p.Glu3Lys (c.7G>A) is classified Benign in ATF4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1886); Low-frequency (popmax 1.07%, eas).

How common is ATF4 p.Glu3Lys (c.7G>A) in the general population?

ATF4 p.Glu3Lys (c.7G>A) is low-frequency (popmax 1.07%, eas) (gnomAD).

What do computational predictors say about ATF4 p.Glu3Lys (c.7G>A)?

AlphaMissense predicts likely benign (score 0.1886) — an in-silico prediction, not a clinical call.

ATF4 p.Glu3Lys

c.7G>A · rs149908720 · VCV725766

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1886 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1886	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.29	unconstrained · MANE · 1,153 bp · p 2.5e-09 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.07% East Asian · 471/44,028 alleles

Filtering AF 0.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.958%

Overall 0.0379% 584/1,542,284 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.07%	93
Remaining individualsnot grpmax-eligible	0.152%	656
Admixed American	0.0164%	6,083
South Asian	0.0135%	7,428
African / African-American	0.00138%	72,410
European (non-Finnish)	0.000262%	381,260

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: ATF4
Protein: p.Glu3Lys
Coding: c.7G>A
MANE Select: NM_182810
dbSNP: rs149908720
Type: single nucleotide variant
Location: chr22:39521452 (GRCh38)
Gene constraint: LOEUF 0.718 · pLI 0.38 (gnomAD)
Structure: AlphaFold pLDDT 62.95 · 2 PDB

Full ATF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF4 p.Ala324Val Benign ★★ same type
ATF4 p.Asn131= Benign ★★ same type
ATF4 p.Glu322Asp Benign ★★ ⚠ same type
ATF4 p.Ile208Met Likely benign ★★ ⚠ same type
ATF4 p.Pro258Ala Benign ★★ same type
ATF4 p.Thr137Ser Likely benign ★★ same type
ATF4 p.Tyr200= Benign ★★ same type
ATF4 p.Val201Ile Benign ★★ 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/atf4-p-glu3lys (accessed [today's date]).

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