Is DDIT4 p.His91Arg (c.272A>G) pathogenic?

DDIT4 p.His91Arg (c.272A>G) is classified Uncertain significance in DDIT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0973); Absent from gnomAD v4.1.

How common is DDIT4 p.His91Arg (c.272A>G) in the general population?

DDIT4 p.His91Arg (c.272A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDIT4 p.His91Arg (c.272A>G)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

DDIT4 p.His91Arg

c.272A>G · VCV4658921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -3.23	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 7.8	GERP 0.36, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 968 bp · p 0.3 · regional, not allelic
Overall
CADD	18.04	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

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.His91Arg
Coding: c.272A>G
MANE Select: NM_019058
Type: single nucleotide variant
Location: chr10:72274761 (GRCh38)
Gene constraint: LOEUF 1.475 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.50 · 2 PDB
Residue 91: an α-helix

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-his91arg (accessed [today's date]).

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