Is DDIT4 p.Ser159Arg (c.477C>G) pathogenic?

DDIT4 p.Ser159Arg (c.477C>G) is classified Uncertain significance in DDIT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: ambiguous (0.3502); Absent from gnomAD v4.1.

How common is DDIT4 p.Ser159Arg (c.477C>G) in the general population?

DDIT4 p.Ser159Arg (c.477C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDIT4 p.Ser159Arg (c.477C>G)?

AlphaMissense predicts ambiguous (score 0.3502) — an in-silico prediction, not a clinical call.

DDIT4 p.Ser159Arg

c.477C>G · rs2494715540 · VCV2238649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3502 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3502	ambiguous
REVEL	0.161	moderately benign-leaning
SaProt	LLR -5.92	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -0.73, phastCons 0.059
Regional constraint	o/e 1.06	unconstrained · MANE · 968 bp · p 0.3 · regional, not allelic
Overall
CADD	19.37	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DDIT4
Protein: p.Ser159Arg
Coding: c.477C>G
MANE Select: NM_019058
dbSNP: rs2494715540
Type: single nucleotide variant
Location: chr10:72274966 (GRCh38)
Gene constraint: LOEUF 1.475 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.50 · 2 PDB
Residue 159: a β-strand

Full DDIT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDIT4 p.Arg108Gln Uncertain significance ★ ⚠ same type
DDIT4 p.Arg113Leu Uncertain significance ★ ⚠ same type
DDIT4 p.Arg133Cys Uncertain significance ★ same type
DDIT4 p.Arg180Cys Uncertain significance ★ ⚠ same type
DDIT4 p.Arg28Trp Uncertain significance ★ ⚠ same type
DDIT4 p.Asn95Ser Uncertain significance ★ ⚠ same type
DDIT4 p.Asp148Asn Uncertain significance ★ ⚠ same type
DDIT4 p.Cys232Arg 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/ddit4-p-ser159arg (accessed [today's date]).

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