Is DPM1 p.Ser28Leu (c.83C>T) pathogenic?

DPM1 p.Ser28Leu (c.83C>T) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely pathogenic (0.9439); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Ser28Leu (c.83C>T)?

DPM1 p.Ser28Leu (c.83C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DPM1 p.Ser28Leu (c.83C>T) in the general population?

DPM1 p.Ser28Leu (c.83C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DPM1 p.Ser28Leu (c.83C>T)?

AlphaMissense predicts likely pathogenic (score 0.9439) — an in-silico prediction, not a clinical call.

DPM1 p.Ser28Leu

c.83C>T · VCV3273606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9439	likely pathogenic
REVEL	0.675	pathogenic-leaning
SaProt	LLR -18.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.19 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,180,042 alleles

Overall 0.000657% 1/152,178 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.Ser28Leu
Coding: c.83C>T
MANE Select: NM_003859
Type: single nucleotide variant
Location: chr20:50958441 (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

Similar variants

DPM1 p.Arg12Met Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg191Gln Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg20Leu Uncertain significance ★★ ⚠ same condition
DPM1 p.Arg216Gln Uncertain significance ★★ ⚠ same condition
DPM1 p.Glu193Asp Uncertain significance ★★ ⚠ same condition
DPM1 p.Glu79Gln Uncertain significance ★★ ⚠ same condition
DPM1 p.Ile128Val Uncertain significance ★★ ⚠ same condition
DPM1 p.Ile56Val 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-ser28leu (accessed [today's date]).

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