Is DDIT4 p.Arg28Trp (c.82C>T) pathogenic?

DDIT4 p.Arg28Trp (c.82C>T) is classified Uncertain significance in DDIT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-19). AlphaMissense: likely benign (0.1106); Very rare (popmax 0.00695%, nfe).

How common is DDIT4 p.Arg28Trp (c.82C>T) in the general population?

DDIT4 p.Arg28Trp (c.82C>T) is very rare (popmax 0.00695%, nfe) (gnomAD).

What do computational predictors say about DDIT4 p.Arg28Trp (c.82C>T)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

DDIT4 p.Arg28Trp

c.82C>T · rs199914945 · VCV2516932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.91	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 1.6	GERP -0.89, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 968 bp · p 0.3 · regional, not allelic
Overall
CADD	23.1	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 0.00695% European (non-Finnish) · 82/1,179,956 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00558% 90/1,613,316 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0096%	10,416
European (non-Finnish)grpmax	0.00695%	14,390
African / African-American	0.00133%	75,062
South Asian	0.0011%	91,080

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg28Trp
Coding: c.82C>T
MANE Select: NM_019058
dbSNP: rs199914945
Type: single nucleotide variant
Location: chr10:72274298 (GRCh38)
Gene constraint: LOEUF 1.475 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.50 · 2 PDB
Residue 28: 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.Asn95Ser Uncertain significance ★ ⚠ same type
DDIT4 p.Asp148Asn Uncertain significance ★ ⚠ same type
DDIT4 p.Cys232Arg Uncertain significance ★ ⚠ same type
DDIT4 p.Glu138Gly 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-arg28trp (accessed [today's date]).

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