Is ATF5 p.Gln193Pro (c.578A>C) pathogenic?

ATF5 p.Gln193Pro (c.578A>C) is classified Uncertain significance in ATF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: likely benign (0.0523); Ultra-rare (popmax 0.0195%, nfe).

How common is ATF5 p.Gln193Pro (c.578A>C) in the general population?

ATF5 p.Gln193Pro (c.578A>C) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

What do computational predictors say about ATF5 p.Gln193Pro (c.578A>C)?

AlphaMissense predicts likely benign (score 0.0523) — an in-silico prediction, not a clinical call.

ATF5 p.Gln193Pro

c.578A>C · rs771872102 · VCV2600228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0523 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0523	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -3.16	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 -1.8	GERP -2.1
Regional constraint	o/e 1.11	unconstrained · MANE · 2,238 bp · p 0.031 · regional, not allelic
Overall
CADD	0.025	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 0.0195% European (non-Finnish) · 230/1,178,198 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0158% 254/1,609,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,123
Admixed American	0.0152%	6,593
Remaining individualsnot grpmax-eligible	0.0128%	7,783
African / African-American	0.00807%	12,389
South Asian	0.00111%	90,226

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.Gln193Pro
Coding: c.578A>C
MANE Select: NM_001193646
dbSNP: rs771872102
Type: single nucleotide variant
Location: chr19:49932821 (GRCh38)
Gene constraint: LOEUF 1.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.00
Residue 193: the 'interaction with ptp4a1' region; the 'disordered' region

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

Similar variants

ATF5 p.Leu30= Benign ★★ same type
ATF5 p.Pro85= 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.Glu110Gln Uncertain significance ★ ⚠ same type
ATF5 p.Glu110Gly Uncertain significance ★ ⚠ same type
ATF5 p.Gly45Val 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-gln193pro (accessed [today's date]).

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