Is ATF5 p.Pro123Arg (c.368C>G) pathogenic?

ATF5 p.Pro123Arg (c.368C>G) is classified Uncertain significance in ATF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.1959); Absent from gnomAD v4.1.

How common is ATF5 p.Pro123Arg (c.368C>G) in the general population?

ATF5 p.Pro123Arg (c.368C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATF5 p.Pro123Arg (c.368C>G)?

AlphaMissense predicts likely benign (score 0.1959) — an in-silico prediction, not a clinical call.

ATF5 p.Pro123Arg

c.368C>G · VCV3320465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1959 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,550,938)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1959	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -9.87	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 4.1	GERP -0.089, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 2,238 bp · p 0.031 · regional, not allelic
Overall
CADD	16.51	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

No allele count reported in gnomAD v4.1 (AN 1,550,938). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATF5
Protein: p.Pro123Arg
Coding: c.368C>G
MANE Select: NM_001193646
Type: single nucleotide variant
Location: chr19:49932611 (GRCh38)
Gene constraint: LOEUF 1.596 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.00
Residue 123: the 'disordered' region; the 'interaction with ptp4a1' 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.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-pro123arg (accessed [today's date]).

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