Is ATF5 p.Pro85= (c.255C>A) pathogenic?

ATF5 p.Pro85= (c.255C>A) is classified Benign in ATF5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-02-20). Common (popmax 9.45%, afr) — too common for a highly-penetrant pathogenic allele.

ATF5 p.Pro85=

Q: How common is ATF5 p.Pro85= (c.255C>A) in the general population?

ATF5 p.Pro85= (c.255C>A) is common (popmax 9.45%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.255C>A · rs1152227 · VCV781515

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 9.45%, 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 -0.7	GERP -2
Overall
CADD	0.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.45% African / African-American · 6,876/72,796 alleles

Filtering AF 9.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.18%

Overall 0.496% 7,963/1,605,344 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.45%	11
Remaining individualsnot grpmax-eligible	0.692%	144
Admixed American	0.563%	178
Middle Eastern	0.403%	248
South Asian	0.17%	589
Ashkenazi Jewishnot grpmax-eligible	0.0407%	2,459
European (non-Finnish)	0.0109%	9,182
East Asian	0.00448%	22,336

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: ATF5
Protein: p.Pro85=
Coding: c.255C>A
MANE Select: NM_001193646
dbSNP: rs1152227
Type: single nucleotide variant
Location: chr19:49932498 (GRCh38)
Gene constraint: LOEUF 1.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.00

Full ATF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATF5 p.Pro85Ala Uncertain significance ★ ⚠ same residue
ATF5 p.Leu30= Benign ★★ same type
ATF5 p.Ala102Gly Uncertain significance ★ ⚠ same type
ATF5 p.Ala35Thr Uncertain significance ★ ⚠ same type
ATF5 p.Arg253Trp Uncertain significance ★ ⚠ same type
ATF5 p.Gln193Pro Uncertain significance ★ ⚠ same type
ATF5 p.Glu110Gln Uncertain significance ★ ⚠ same type
ATF5 p.Glu110Gly 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/atf5-p-pro85 (accessed [today's date]).

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