Is ATF3 p.His53= (c.159C>T) pathogenic?

ATF3 p.His53= (c.159C>T) is classified Likely benign in ATF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). Very rare (popmax 0.00668%, eas).

How common is ATF3 p.His53= (c.159C>T) in the general population?

ATF3 p.His53= (c.159C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

ATF3 p.His53=

c.159C>T · rs747811798 · VCV2602380

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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 1.7	GERP 2.2, phastCons 1
Overall
CADD	11.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,880 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000274% 4/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,960
European (non-Finnish)	8.47e-05%	1,180,054

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: ATF3
Protein: p.His53=
Coding: c.159C>T
MANE Select: NM_001674
dbSNP: rs747811798
Type: single nucleotide variant
Location: chr1:212615180 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 77.45

Full ATF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF3 p.Ser12Pro Uncertain significance ★★ ⚠ same type
ATF3 p.Ala82Val Uncertain significance ★ ⚠ same type
ATF3 p.Asn168Ile Uncertain significance ★ ⚠ same type
ATF3 p.Asp69Asn Uncertain significance ★ ⚠ same type
ATF3 p.Gln115Glu Uncertain significance ★ ⚠ same type
ATF3 p.Glu32Lys Uncertain significance ★ ⚠ same type
ATF3 p.Glu80Lys Uncertain significance ★ ⚠ same type
ATF3 p.Ile171Thr Uncertain significance ★ ⚠ 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/atf3-p-his53 (accessed [today's date]).

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