Is DPM1 p.Pro129Ser (c.385C>T) pathogenic?

DPM1 p.Pro129Ser (c.385C>T) is classified Uncertain significance in DPM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). AlphaMissense: likely benign (0.255); Very rare (popmax 0.00304%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Pro129Ser (c.385C>T)?

DPM1 p.Pro129Ser (c.385C>T) is associated with Inborn genetic diseases, congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Pro129Ser (c.385C>T) in the general population?

DPM1 p.Pro129Ser (c.385C>T) is very rare (popmax 0.00304%, nfe) (gnomAD).

What do computational predictors say about DPM1 p.Pro129Ser (c.385C>T)?

AlphaMissense predicts likely benign (score 0.255) — an in-silico prediction, not a clinical call.

DPM1 p.Pro129Ser

c.385C>T · rs752831768 · VCV650177

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00304%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.255	likely benign
REVEL	0.507	indeterminate
SaProt	LLR -8.92	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.38	donor loss · deltas
Pangolin	Δ0.31	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.19 · regional, not allelic
Overall
CADD	26.7	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

Grpmax group 0.00304% European (non-Finnish) · 35/1,152,152 alleles

Filtering AF 0.00221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00221% 35/1,581,966 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: DPM1
Protein: p.Pro129Ser
Coding: c.385C>T
MANE Select: NM_003859
dbSNP: rs752831768
Type: single nucleotide variant
Location: chr20:50945750 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.61

Full DPM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital disorder of glycosylation type 1E

Similar variants

DPM1 p.Pro129Thr Uncertain significance ★★ ⚠ same residue
DPM1 p.Arg92Gly Pathogenic ★★ same condition
DPM1 p.His124Arg Likely pathogenic ★★ same condition
DPM1 p.Met1Leu Pathogenic/Likely pathogenic ★★ same condition
DPM1 c.*12T>C Uncertain significance ★★ same condition
DPM1 p.Ala109Val Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg12Met Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg191Gln Uncertain significance ★★ ⚠ same condition

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/dpm1-p-pro129ser (accessed [today's date]).

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