Is DPM3 p.Ala86Val (c.257C>T) pathogenic?

DPM3 p.Ala86Val (c.257C>T) is classified Uncertain significance in DPM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-16). AlphaMissense: likely benign (0.1088); Very rare (popmax 0.0022%, sas).

How common is DPM3 p.Ala86Val (c.257C>T) in the general population?

DPM3 p.Ala86Val (c.257C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about DPM3 p.Ala86Val (c.257C>T)?

AlphaMissense predicts likely benign (score 0.1088) — an in-silico prediction, not a clinical call.

DPM3 p.Ala86Val

c.257C>T · rs752119871 · VCV2238032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1088	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -8.47	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 4.2	GERP -1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 275 bp · p 0.45 · regional, not allelic
Overall
CADD	16.63	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 0.0022% South Asian · 2/91,014 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000205% 3/1,460,454 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,507
European (non-Finnish)	8.48e-05%	1,179,368

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: DPM3
Protein: p.Ala86Val
Coding: c.257C>T
MANE Select: NM_153741
dbSNP: rs752119871
Type: single nucleotide variant
Location: chr1:155139984 (GRCh38)
Gene constraint: LOEUF 1.364 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.73
Residue 86: a UniProt-annotated variant site (in mddgb15; uncertain significance)

Full DPM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPM3 p.Ala86Asp Uncertain significance ★★ ⚠ same residue
DPM3 p.Ala70Thr Uncertain significance ★★ ⚠ same type
DPM3 p.Arg60Cys Uncertain significance ★★ ⚠ same type
DPM3 p.Arg60Leu Uncertain significance ★★ ⚠ same type
DPM3 p.Gln6His Uncertain significance ★★ ⚠ same type
DPM3 p.Glu73Ala Uncertain significance ★★ ⚠ same type
DPM3 p.Gly50Ser Uncertain significance ★★ ⚠ same type
DPM3 p.Gly89Glu 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/dpm3-p-ala86val (accessed [today's date]).

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