Is DPM1 p.Pro129Thr (c.385C>A) pathogenic?

DPM1 p.Pro129Thr (c.385C>A) is classified Uncertain significance in DPM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-04). AlphaMissense: likely benign (0.2049); Ultra-rare (popmax 0.0877%, afr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Pro129Thr (c.385C>A)?

DPM1 p.Pro129Thr (c.385C>A) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Pro129Thr (c.385C>A) in the general population?

DPM1 p.Pro129Thr (c.385C>A) is ultra-rare (popmax 0.0877%, afr) (gnomAD).

How is DPM1-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DPM1 p.Pro129Thr (c.385C>A)?

AlphaMissense predicts likely benign (score 0.2049) — an in-silico prediction, not a clinical call.

DPM1 p.Pro129Thr

c.385C>A · rs752831768 · VCV572012

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0877%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.2049	likely benign
REVEL	0.858	moderately pathogenic-leaning
SaProt	LLR -9.68	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.32	donor loss · deltas
Pangolin	Δ0.24	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	31.0	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 0.0877% African / African-American · 65/74,076 alleles

Filtering AF 0.0706% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0644%

Overall 0.0048% 76/1,581,968 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0877%	1,140
Middle Eastern	0.0192%	5,208
Remaining individualsnot grpmax-eligible	0.00815%	12,270
Admixed American	0.00501%	19,977
European (non-Finnish)	0.000174%	576,077

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.Pro129Thr
Coding: c.385C>A
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

congenital disorder of glycosylation type 1E — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DPM1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DPM1 p.Pro129Ser 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-pro129thr (accessed [today's date]).

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