Is DPM1 p.Arg92Ter (c.274C>T) pathogenic?

DPM1 p.Arg92Ter (c.274C>T) is classified Likely pathogenic in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-07). Very rare (popmax 0.00134%, afr).

How common is DPM1 p.Arg92Ter (c.274C>T) in the general population?

DPM1 p.Arg92Ter (c.274C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

DPM1 p.Arg92Ter

c.274C>T · rs121908583 · VCV1343000

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 9
REVEL	0.376	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,874 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,613,660 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,986
African / African-Americangrpmax	0.00134%	74,874
European (non-Finnish)	0.000339%	294,942

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg92Ter
Coding: c.274C>T
MANE Select: NM_003859
dbSNP: rs121908583
Type: single nucleotide variant
Location: chr20:50948650 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.61
Residue 92: a UniProt-annotated variant site (in cdg1e)

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

Similar variants

DPM1 p.Arg92Gly Pathogenic ★★ same residue
DPM1 p.Arg92Gln Uncertain significance ★ ⚠ same residue
DPM1 p.Arg92= Likely benign ★ same residue
DPM1 p.His124Arg Likely pathogenic ★★ same type
DPM1 p.Met1Leu Pathogenic/Likely pathogenic ★★ same type
DPM1 c.*12T>C Uncertain significance ★★ same type
DPM1 p.Ala109Val Uncertain significance ★★ ⚠ same type
DPM1 p.Arg12Met Uncertain significance ★★ ⚠ same type

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-arg92ter (accessed [today's date]).

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