Is DPM1 p.Ile114Val (c.340A>G) pathogenic?

DPM1 p.Ile114Val (c.340A>G) is classified Uncertain significance in DPM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0963); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPM1 p.Ile114Val (c.340A>G)?

DPM1 p.Ile114Val (c.340A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DPM1 p.Ile114Val (c.340A>G) in the general population?

DPM1 p.Ile114Val (c.340A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DPM1 p.Ile114Val (c.340A>G)?

AlphaMissense predicts likely benign (score 0.0963) — an in-silico prediction, not a clinical call.

DPM1 p.Ile114Val

c.340A>G · VCV4244447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0963	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.038	GERP -0.54, phastCons 0.073
Regional constraint	o/e 1.09	unconstrained · MANE · 16 kb · p 0.19 · regional, not allelic
Overall
CADD	13.32	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 8.48e-05% European (non-Finnish) · 1/1,179,750 alleles

Overall 6.84e-05% 1/1,461,358 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.Ile114Val
Coding: c.340A>G
MANE Select: NM_003859
Type: single nucleotide variant
Location: chr20:50945879 (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.Ile114Asn Uncertain significance ★ ⚠ same residue
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

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-ile114val (accessed [today's date]).

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