Is DDIT3 p.Ser88Thr (c.263G>C) pathogenic?

DDIT3 p.Ser88Thr (c.263G>C) is classified Uncertain significance in DDIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely benign (0.0994); Ultra-rare (popmax 0.0307%, afr).

How common is DDIT3 p.Ser88Thr (c.263G>C) in the general population?

DDIT3 p.Ser88Thr (c.263G>C) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

What do computational predictors say about DDIT3 p.Ser88Thr (c.263G>C)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

DDIT3 p.Ser88Thr

c.263G>C · rs375020445 · VCV3080760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.33	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 5.8	GERP 2.2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 594 bp · p 0.35 · regional, not allelic
Overall
CADD	24.9	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 0.0307% African / African-American · 23/74,910 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00143% 23/1,614,020 alleles · ultra-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: DDIT3
Protein: p.Ser88Thr
Coding: c.263G>C
MANE Select: NM_004083
dbSNP: rs375020445
Type: single nucleotide variant
Location: chr12:57517056 (GRCh38)
Gene constraint: LOEUF 1.188 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76
Residue 88: the 'disordered' region

Full DDIT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDIT3 c.-23T>C Benign ★★ same type
DDIT3 c.-32-25C>G Benign ★★ same type
DDIT3 p.Glu146Lys Likely benign ★★ same type
DDIT3 c.-15G>A Uncertain significance ★ same type
DDIT3 c.-32-6C>G Uncertain significance ★ same type
DDIT3 c.*17G>A Uncertain significance ★ same type
DDIT3 p.Arg103Lys Uncertain significance ★ ⚠ same type
DDIT3 p.Arg105Gln 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/ddit3-p-ser88thr (accessed [today's date]).

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