Is DPM3 p.Arg87Cys (c.259C>T) pathogenic?

DPM3 p.Arg87Cys (c.259C>T) is classified Uncertain significance in DPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-23). AlphaMissense: likely benign (0.1274); Very rare (popmax 0.00223%, eas).

How common is DPM3 p.Arg87Cys (c.259C>T) in the general population?

DPM3 p.Arg87Cys (c.259C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DPM3 p.Arg87Cys (c.259C>T)?

AlphaMissense predicts likely benign (score 0.1274) — an in-silico prediction, not a clinical call.

DPM3 p.Arg87Cys

c.259C>T · rs1167375466 · VCV3085506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1274 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1274	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -11.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 275 bp · p 0.45 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 0.00223% East Asian · 1/44,804 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00048% 7/1,459,234 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,804
Remaining individualsnot grpmax-eligible	0.0016%	62,386
European (non-Finnish)	0.000424%	235,681

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: DPM3
Protein: p.Arg87Cys
Coding: c.259C>T
MANE Select: NM_153741
dbSNP: rs1167375466
Type: single nucleotide variant
Location: chr1:155139982 (GRCh38)
Gene constraint: LOEUF 1.364 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.73
Residue 87: a UniProt-annotated variant site (in mddgb15; uncertain significance)

Full DPM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPM3 p.Ala70Thr Uncertain significance ★★ ⚠ same type
DPM3 p.Ala86Asp Uncertain significance ★★ ⚠ same type
DPM3 p.Arg60Cys Uncertain significance ★★ ⚠ same type
DPM3 p.Arg60Leu Uncertain significance ★★ ⚠ same type
DPM3 p.Gln6His Uncertain significance ★★ ⚠ same type
DPM3 p.Glu73Ala Uncertain significance ★★ ⚠ same type
DPM3 p.Gly50Ser Uncertain significance ★★ ⚠ same type
DPM3 p.Gly89Glu 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/dpm3-p-arg87cys (accessed [today's date]).

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