Is DDI1 p.Pro367Ser (c.1099C>T) pathogenic?

DDI1 p.Pro367Ser (c.1099C>T) is classified Uncertain significance in DDI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-15). AlphaMissense: ambiguous (0.4198); Ultra-rare (popmax 0.0165%, mid).

How common is DDI1 p.Pro367Ser (c.1099C>T) in the general population?

DDI1 p.Pro367Ser (c.1099C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DDI1 p.Pro367Ser (c.1099C>T)?

AlphaMissense predicts ambiguous (score 0.4198) — an in-silico prediction, not a clinical call.

DDI1 p.Pro367Ser

c.1099C>T · VCV4010003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4198	ambiguous
REVEL	0.414	indeterminate
SaProt	LLR -13.29	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,187 bp · p 0.52 · regional, not allelic
Overall
CADD	23.4	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000137% 2/1,461,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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: DDI1
Protein: p.Pro367Ser
Coding: c.1099C>T
MANE Select: NM_001001711
Type: single nucleotide variant
Location: chr11:104037921 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.27 · 1 PDB

Full DDI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDI1 p.Asp323Asn Benign ★★ same type
DDI1 p.His155= Benign ★★ same type
DDI1 p.Pro41= Benign ★★ same type
DDI1 p.Thr178= Benign ★★ same type
DDI1 p.Ala100Val Uncertain significance ★ ⚠ same type
DDI1 p.Ala36Gly Uncertain significance ★ ⚠ same type
DDI1 p.Ala84Val Uncertain significance ★ ⚠ same type
DDI1 p.Arg108Gly 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/ddi1-p-pro367ser (accessed [today's date]).

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