Is DDIT4 p.Ser52Leu (c.155C>T) pathogenic?

DDIT4 p.Ser52Leu (c.155C>T) is classified Uncertain significance in DDIT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: ambiguous (0.5055); Very rare (popmax 0.00267%, afr).

How common is DDIT4 p.Ser52Leu (c.155C>T) in the general population?

DDIT4 p.Ser52Leu (c.155C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about DDIT4 p.Ser52Leu (c.155C>T)?

AlphaMissense predicts ambiguous (score 0.5055) — an in-silico prediction, not a clinical call.

DDIT4 p.Ser52Leu

c.155C>T · VCV3271202

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
AlphaMissense	0.5055	ambiguous
REVEL	0.294	indeterminate
SaProt	LLR -4.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 968 bp · p 0.3 · regional, not allelic
Overall
CADD	28.4	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

Grpmax group 0.00267% African / African-American · 2/74,824 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,150 alleles · very rare

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: DDIT4
Protein: p.Ser52Leu
Coding: c.155C>T
MANE Select: NM_019058
Type: single nucleotide variant
Location: chr10:72274371 (GRCh38)
Gene constraint: LOEUF 1.475 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.50 · 2 PDB
Residue 52: the 'disordered' region

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-ser52leu (accessed [today's date]).

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