Is DPM1 p.Ile229Val (c.685A>G) pathogenic?

DPM1 p.Ile229Val (c.685A>G) is classified Uncertain significance in DPM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-03-20). AlphaMissense: likely benign (0.2596); Rare (popmax 0.106%, amr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Ile229Val (c.685A>G)?

DPM1 p.Ile229Val (c.685A>G) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Ile229Val (c.685A>G) in the general population?

DPM1 p.Ile229Val (c.685A>G) is rare (popmax 0.106%, amr) (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.Ile229Val (c.685A>G)?

AlphaMissense predicts likely benign (score 0.2596) — an in-silico prediction, not a clinical call.

DPM1 p.Ile229Val

c.685A>G · rs559946698 · VCV565495

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2596 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.106%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.2596	likely benign
REVEL	0.366	indeterminate
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,080 bp · p 0.94 · regional, not allelic
Overall
CADD	25.5	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 0.106% Admixed American · 62/58,438 alleles

Filtering AF 0.0849% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0772%

Overall 0.00769% 122/1,585,922 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.106%	943
Remaining individualsnot grpmax-eligible	0.021%	4,768
African / African-American	0.00809%	12,360
East Asian	0.0045%	22,220
European (non-Finnish)	0.00325%	30,782
South Asian	0.00221%	45,157

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.Ile229Val
Coding: c.685A>G
MANE Select: NM_003859
dbSNP: rs559946698
Type: single nucleotide variant
Location: chr20:50935230 (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.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
DPM1 p.Arg20Leu 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-ile229val (accessed [today's date]).

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