Is DPH2 p.Leu338Pro (c.1013T>C) pathogenic?

DPH2 p.Leu338Pro (c.1013T>C) is classified Uncertain significance in DPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: ambiguous (0.4941); Absent from gnomAD v4.1.

How common is DPH2 p.Leu338Pro (c.1013T>C) in the general population?

DPH2 p.Leu338Pro (c.1013T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPH2 p.Leu338Pro (c.1013T>C)?

AlphaMissense predicts ambiguous (score 0.4941) — an in-silico prediction, not a clinical call.

DPH2 p.Leu338Pro

c.1013T>C · VCV3273591

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4941	ambiguous
REVEL	0.643	indeterminate
SaProt	LLR -11.43	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.18	constrained · MANE · 43 bp · p 0.0009 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPH2
Protein: p.Leu338Pro
Coding: c.1013T>C
MANE Select: NM_001384
Type: single nucleotide variant
Location: chr1:43971915 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60
Residue 338: a UniProt-annotated variant site (in dedssh2; severely impairs diphthamide modification of elongation factor 2)

Full DPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPH2 p.Arg201His Uncertain significance ★★ ⚠ same type
DPH2 p.Arg477Ter Likely pathogenic ★ same type
DPH2 p.Ser75Ter Likely pathogenic ★ same type
DPH2 p.Ala310Val Uncertain significance ★ ⚠ same type
DPH2 p.Ala345Thr Uncertain significance ★ ⚠ same type
DPH2 p.Ala448Thr Uncertain significance ★ ⚠ same type
DPH2 p.Arg125His Uncertain significance ★ ⚠ same type
DPH2 p.Arg169Cys 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/dph2-p-leu338pro (accessed [today's date]).

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