Is DPY30 p.Ala85Val (c.254C>T) pathogenic?

DPY30 p.Ala85Val (c.254C>T) is classified Uncertain significance in DPY30 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.9963); Very rare (popmax 8.48e-05%, nfe).

How common is DPY30 p.Ala85Val (c.254C>T) in the general population?

DPY30 p.Ala85Val (c.254C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DPY30 p.Ala85Val (c.254C>T)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

DPY30 p.Ala85Val

c.254C>T · rs2465552457 · VCV3085636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic
REVEL	0.678	pathogenic-leaning
SaProt	LLR -12.88	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 9.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 67 bp · p 0.29 · regional, not allelic
Overall
CADD	31.0	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 8.48e-05% European (non-Finnish) · 1/1,179,270 alleles

Overall 6.85e-05% 1/1,460,344 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: DPY30
Protein: p.Ala85Val
Coding: c.254C>T
MANE Select: NM_001321209
dbSNP: rs2465552457
Type: single nucleotide variant
Location: chr2:32024230 (GRCh38)
Gene constraint: LOEUF 0.747 · pLI 0.46 (gnomAD)
Structure: AlphaFold pLDDT 75.98 · 12 PDB
Residue 85: an α-helix

Full DPY30 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPY30 p.Arg98Gln Uncertain significance ★ ⚠ same type
DPY30 p.His18Pro Uncertain significance ★ ⚠ same type
DPY30 p.Phe95Ser Uncertain significance ★ ⚠ same type
DPY30 p.Val31Leu 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/dpy30-p-ala85val (accessed [today's date]).

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