Is DDIT3 p.Phe10Ser (c.29T>C) pathogenic?

DDIT3 p.Phe10Ser (c.29T>C) is classified Uncertain significance in DDIT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.1266); Very rare (popmax 0.0022%, sas).

How common is DDIT3 p.Phe10Ser (c.29T>C) in the general population?

DDIT3 p.Phe10Ser (c.29T>C) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DDIT3 p.Phe10Ser (c.29T>C)?

AlphaMissense predicts likely benign (score 0.1266) — an in-silico prediction, not a clinical call.

DDIT3 p.Phe10Ser

c.29T>C · VCV4238420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1266 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1266	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -4.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.25 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 594 bp · p 0.35 · regional, not allelic
Overall
CADD	21.7	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 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,611,824 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
European (non-Finnish)	0.000593%	168,573

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.Phe10Ser
Coding: c.29T>C
MANE Select: NM_004083
Type: single nucleotide variant
Location: chr12:57517378 (GRCh38)
Gene constraint: LOEUF 1.188 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76
Residue 10: the 'n-terminal' region; the 'interaction with trib3' 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-phe10ser (accessed [today's date]).

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