DPM2 p.Tyr71=

Q: Is DPM2 p.Tyr71= (c.213T>C) pathogenic?

DPM2 p.Tyr71= (c.213T>C) is classified Benign in DPM2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 87.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with congenital muscular dystrophy with intellectual disability and severe epilepsy.

Q: What condition is associated with DPM2 p.Tyr71= (c.213T>C)?

DPM2 p.Tyr71= (c.213T>C) is associated with congenital muscular dystrophy with intellectual disability and severe epilepsy (ClinVar).

Q: How common is DPM2 p.Tyr71= (c.213T>C) in the general population?

DPM2 p.Tyr71= (c.213T>C) is common (popmax 87.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Congenital muscular dystrophy with intellectual disability and severe epilepsy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.213T>C · rs6781 · VCV128920

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 87.4%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

congenital muscular dystrophy with intellectual disability and severe epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.63 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.2	GERP -4.6
Overall
CADD	1.798	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 87.4% European (non-Finnish) · 1,028,786/1,176,890 alleles

Filtering AF 87.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 87.2%

Overall 84.4% 1,359,015/1,610,162 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	91.9%	1
Finnishnot grpmax-eligible	89.8%	1
European (non-Finnish)grpmax	87.4%	1
Admixed American	86.2%	1
Remaining individualsnot grpmax-eligible	82.1%	1
Middle Eastern	74.4%	1
Ashkenazi Jewishnot grpmax-eligible	72.9%	1
South Asian	71.2%	1
African / African-American	67.4%	1
East Asian	62.3%	2

Amish 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: DPM2
Protein: p.Tyr71=
Coding: c.213T>C
MANE Select: NM_003863
dbSNP: rs6781
Type: single nucleotide variant
Location: chr9:127935764 (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

Disease context

congenital muscular dystrophy with intellectual disability and severe epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital muscular dystrophy with intellectual disability and severe epilepsy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DPM2 p.Tyr71Cys Uncertain significance ★ ⚠ same residue
DPM2 p.Arg47Ter Pathogenic/Likely pathogenic ★★ same condition
DPM2 p.Ala52Thr Uncertain significance ★★ ⚠ same condition
DPM2 p.Leu30Val Uncertain significance ★★ ⚠ same condition
DPM2 p.Leu62Val Uncertain significance ★★ ⚠ same condition
DPM2 p.Tyr43His Uncertain significance ★★ same condition
DPM2 p.Val51Ile Uncertain significance ★★ ⚠ same condition
DPM2 c.3+12A>G Benign/Likely benign ★★ 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/dpm2-p-tyr71 (accessed [today's date]).

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