Is DPYS p.Asp24His (c.70G>C) pathogenic?

DPYS p.Asp24His (c.70G>C) is classified Uncertain significance in DPYS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). AlphaMissense: likely pathogenic (0.8342); Very rare (popmax 0.00394%, amr).

How common is DPYS p.Asp24His (c.70G>C) in the general population?

DPYS p.Asp24His (c.70G>C) is very rare (popmax 0.00394%, amr) (gnomAD).

What do computational predictors say about DPYS p.Asp24His (c.70G>C)?

AlphaMissense predicts likely pathogenic (score 0.8342) — an in-silico prediction, not a clinical call.

DPYS p.Asp24His

c.70G>C · rs1019808073 · VCV1928253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8342 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00394%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8342	likely pathogenic
REVEL	0.816	moderately pathogenic-leaning
SaProt	LLR -12.22	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00394% Admixed American · 2/50,710 alleles

Filtering AF 0.000654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000245%

Overall 0.000131% 2/1,531,272 alleles · very rare

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: DPYS
Protein: p.Asp24His
Coding: c.70G>C
MANE Select: NM_001385
dbSNP: rs1019808073
Type: single nucleotide variant
Location: chr8:104466851 (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 24: a β-strand

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-asp24his (accessed [today's date]).

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