Is DPM1 p.Arg166His (c.497G>A) pathogenic?

DPM1 p.Arg166His (c.497G>A) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: ambiguous (0.3879); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Arg166His (c.497G>A)?

DPM1 p.Arg166His (c.497G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPM1 p.Arg166His (c.497G>A) in the general population?

DPM1 p.Arg166His (c.497G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about DPM1 p.Arg166His (c.497G>A)?

AlphaMissense predicts ambiguous (score 0.3879) — an in-silico prediction, not a clinical call.

DPM1 p.Arg166His

c.497G>A · VCV4014581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3879	ambiguous
REVEL	0.429	indeterminate
SaProt	LLR -11.77	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 0.93, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 5,851 bp · p 0.0004 · regional, not allelic
Overall
CADD	28.4	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 0.000339% European (non-Finnish) · 4/1,179,816 alleles

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

Overall 0.000248% 4/1,613,424 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.Arg166His
Coding: c.497G>A
Type: single nucleotide variant
Location: chr20:50940931 (GRCh38)

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

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-arg166his (accessed [today's date]).

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