Is ATF5 p.Pro85Ala (c.253C>G) pathogenic?

ATF5 p.Pro85Ala (c.253C>G) is classified Uncertain significance in ATF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.0461); Rare (popmax 0.214%, afr).

How common is ATF5 p.Pro85Ala (c.253C>G) in the general population?

ATF5 p.Pro85Ala (c.253C>G) is rare (popmax 0.214%, afr) (gnomAD).

What do computational predictors say about ATF5 p.Pro85Ala (c.253C>G)?

AlphaMissense predicts likely benign (score 0.0461) — an in-silico prediction, not a clinical call.

ATF5 p.Pro85Ala

c.253C>G · rs144477617 · VCV2213643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0461 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0461	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.39	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 -0.19	GERP -2, phastCons 0.026
Regional constraint	o/e 1.11	unconstrained · MANE · 2,238 bp · p 0.031 · regional, not allelic
Overall
CADD	0.507	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% African / African-American · 159/74,382 alleles

Filtering AF 0.187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.0103% 166/1,608,676 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.214%	468
Remaining individualsnot grpmax-eligible	0.00802%	12,466
Finnishnot grpmax-eligible	0.00157%	63,670
European (non-Finnish)	8.5e-05%	1,176,525

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.Pro85Ala
Coding: c.253C>G
MANE Select: NM_001193646
dbSNP: rs144477617
Type: single nucleotide variant
Location: chr19:49932496 (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.Pro85= Benign ★★ 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-pro85ala (accessed [today's date]).

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