Is DPM2 p.Ala56Ser (c.166G>T) pathogenic?

DPM2 p.Ala56Ser (c.166G>T) is classified Uncertain significance in DPM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: likely benign (0.1322); Ultra-rare (popmax 0.0171%, mid).

How common is DPM2 p.Ala56Ser (c.166G>T) in the general population?

DPM2 p.Ala56Ser (c.166G>T) is ultra-rare (popmax 0.0171%, mid) (gnomAD).

What do computational predictors say about DPM2 p.Ala56Ser (c.166G>T)?

AlphaMissense predicts likely benign (score 0.1322) — an in-silico prediction, not a clinical call.

DPM2 p.Ala56Ser

c.166G>T · rs377060098 · VCV2465764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1322 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1322	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,095 bp · p 0.35 · regional, not allelic
Overall
CADD	20.4	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 0.0171% Middle Eastern · 1/5,864 alleles

Filtering AF 0.00093% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000458%

Overall 0.000894% 14/1,566,632 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,864
Remaining individualsnot grpmax-eligible	0.00829%	12,060
South Asian	0.0035%	28,549
East Asian	0.00232%	43,182
European (non-Finnish)	0.000347%	288,376

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: DPM2
Protein: p.Ala56Ser
Coding: c.166G>T
MANE Select: NM_003863
dbSNP: rs377060098
Type: single nucleotide variant
Location: chr9:127936583 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.96

Full DPM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DPM2 p.Ala56Val Uncertain significance ★ ⚠ same residue
DPM2 p.Ala56Phe Uncertain significance ★★ same residue
DPM2 p.Arg47Ter Pathogenic/Likely pathogenic ★★ same type
DPM2 p.Ala52Thr Uncertain significance ★★ ⚠ same type
DPM2 p.Leu30Val Uncertain significance ★★ ⚠ same type
DPM2 p.Leu62Val Uncertain significance ★★ ⚠ same type
DPM2 p.Tyr43His Uncertain significance ★★ ⚠ same type
DPM2 p.Val51Ile 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/dpm2-p-ala56ser (accessed [today's date]).

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