Is DPM1 p.Val208Ile (c.622G>A) pathogenic?

DPM1 p.Val208Ile (c.622G>A) is classified Uncertain significance in DPM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-27). AlphaMissense: likely benign (0.1431); Very rare (popmax 0.00133%, afr); Associated with congenital disorder of glycosylation type 1E.

What condition is associated with DPM1 p.Val208Ile (c.622G>A)?

DPM1 p.Val208Ile (c.622G>A) is associated with congenital disorder of glycosylation type 1E (ClinVar).

How common is DPM1 p.Val208Ile (c.622G>A) in the general population?

DPM1 p.Val208Ile (c.622G>A) is very rare (popmax 0.00133%, 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.Val208Ile (c.622G>A)?

AlphaMissense predicts likely benign (score 0.1431) — an in-silico prediction, not a clinical call.

DPM1 p.Val208Ile

c.622G>A · rs938379512 · VCV898456

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1431 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital disorder of glycosylation type 1E

Computational evidence

Protein change
AlphaMissense	0.1431	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -7.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 0.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,080 bp · p 0.94 · regional, not allelic
Overall
CADD	24.0	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 0.00133% African / African-American · 1/74,928 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000806% 13/1,613,622 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,928
European (non-Finnish)	0.00102%	98,318

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.Val208Ile
Coding: c.622G>A
dbSNP: rs938379512
Type: single nucleotide variant
Location: chr20:50936204 (GRCh38)

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

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-val208ile (accessed [today's date]).

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