Is DPYS p.Val349Leu (c.1045G>T) pathogenic?

DPYS p.Val349Leu (c.1045G>T) is classified Uncertain significance in DPYS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: ambiguous (0.3633); Absent from gnomAD v4.1.

How common is DPYS p.Val349Leu (c.1045G>T) in the general population?

DPYS p.Val349Leu (c.1045G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPYS p.Val349Leu (c.1045G>T)?

AlphaMissense predicts ambiguous (score 0.3633) — an in-silico prediction, not a clinical call.

DPYS p.Val349Leu

c.1045G>T · rs2537770233 · VCV2011871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3633 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3633	ambiguous
REVEL	0.419	indeterminate
SaProt	LLR -12.01	damaging
Splicing
SpliceAI	Δ0.20	donor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	22.6	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: DPYS
Protein: p.Val349Leu
Coding: c.1045G>T
MANE Select: NM_001385
dbSNP: rs2537770233
Type: single nucleotide variant
Location: chr8:104428027 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 1 PDB

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

Similar variants

DPYS c.424-1G>A Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg302Gln Likely pathogenic ★★ same type
DPYS p.Arg302Ter Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg465Ter Pathogenic ★★ same type
DPYS p.Arg475Ter Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg490Cys Pathogenic/Likely pathogenic ★★ same type
DPYS p.Arg490His Pathogenic/Likely pathogenic ★★ same type
DPYS p.Gln190Ter Pathogenic ★★ 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/dpys-p-val349leu (accessed [today's date]).

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