Is DDI2 p.His119Arg (c.356A>G) pathogenic?

DDI2 p.His119Arg (c.356A>G) is classified Uncertain significance in DDI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely benign (0.0585); Rare (popmax 0.159%, sas).

How common is DDI2 p.His119Arg (c.356A>G) in the general population?

DDI2 p.His119Arg (c.356A>G) is rare (popmax 0.159%, sas) (gnomAD).

What do computational predictors say about DDI2 p.His119Arg (c.356A>G)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

DDI2 p.His119Arg

c.356A>G · rs532223617 · VCV2269465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.159%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -5.22	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 0.28	GERP -3, phastCons 0.055
Regional constraint	o/e 0.63	unconstrained · MANE · 16 kb · p 1.3e-08 · regional, not allelic
Overall
CADD	10.09	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 0.159% South Asian · 145/91,082 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.13%

Overall 0.00979% 158/1,614,156 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.159%	628
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.008%	12,502
East Asian	0.00223%	44,880
European (non-Finnish)	0.000254%	393,342

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: DDI2
Protein: p.His119Arg
Coding: c.356A>G
MANE Select: NM_032341
dbSNP: rs532223617
Type: single nucleotide variant
Location: chr1:15630412 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.85 · 3 PDB
Residue 119: the 'disordered' region

Full DDI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDI2 p.Ala394Pro Uncertain significance ★ ⚠ same type
DDI2 p.Arg108Gln Uncertain significance ★ ⚠ same type
DDI2 p.Arg108Trp Uncertain significance ★ ⚠ same type
DDI2 p.Arg110His Uncertain significance ★ ⚠ same type
DDI2 p.Arg139Ter Uncertain significance ★ same type
DDI2 p.Arg173Gly Uncertain significance ★ ⚠ same type
DDI2 p.Arg184Gln Uncertain significance ★ ⚠ same type
DDI2 p.Arg277Gln 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/ddi2-p-his119arg (accessed [today's date]).

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