Is DPYS p.Leu52Phe (c.154C>T) pathogenic?

DPYS p.Leu52Phe (c.154C>T) is classified Uncertain significance in DPYS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). AlphaMissense: likely benign (0.251); Absent from gnomAD v4.1.

How common is DPYS p.Leu52Phe (c.154C>T) in the general population?

DPYS p.Leu52Phe (c.154C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPYS p.Leu52Phe (c.154C>T)?

AlphaMissense predicts likely benign (score 0.251) — an in-silico prediction, not a clinical call.

DPYS p.Leu52Phe

c.154C>T · VCV4742997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.251 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,576)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.251	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP -3.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	23.5	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

No allele count reported in gnomAD v4.1 (AN 1,534,576). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DPYS
Protein: p.Leu52Phe
Coding: c.154C>T
MANE Select: NM_001385
Type: single nucleotide variant
Location: chr8:104466767 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 1 PDB
Residue 52: a β-strand

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

Similar variants

DPYS p.Leu52= Likely benign ★ same residue
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

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-leu52phe (accessed [today's date]).

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