Is DSE p.Trp948Arg (c.2842T>C) pathogenic?

DSE p.Trp948Arg (c.2842T>C) is classified Uncertain significance in DSE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). AlphaMissense: likely pathogenic (0.8183); Ultra-rare (popmax 0.018%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DSE p.Trp948Arg (c.2842T>C)?

DSE p.Trp948Arg (c.2842T>C) is associated with Inborn genetic diseases, Ehlers-Danlos syndrome, musculocontractural type, Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

How common is DSE p.Trp948Arg (c.2842T>C) in the general population?

DSE p.Trp948Arg (c.2842T>C) is ultra-rare (popmax 0.018%, nfe) (gnomAD).

What do computational predictors say about DSE p.Trp948Arg (c.2842T>C)?

AlphaMissense predicts likely pathogenic (score 0.8183) — an in-silico prediction, not a clinical call.

DSE p.Trp948Arg

c.2842T>C · rs146336077 · VCV450141

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.8183 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8183	likely pathogenic
REVEL	0.35	indeterminate
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 870 bp · p 0.076 · regional, not allelic
Overall
CADD	24.0	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 0.018% European (non-Finnish) · 212/1,179,692 alleles

Filtering AF 0.016% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0152%

Overall 0.0138% 222/1,613,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.018%	5,565
Remaining individualsnot grpmax-eligible	0.00801%	12,491
African / African-American	0.00401%	24,955
Finnishnot grpmax-eligible	0.00313%	31,992

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: DSE
Protein: p.Trp948Arg
Coding: c.2842T>C
MANE Select: NM_013352
dbSNP: rs146336077
Type: single nucleotide variant
Location: chr6:116437310 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.06 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.59 · 1 PDB

Full DSE 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

Also linked: Ehlers-Danlos syndrome, musculocontractural type Ehlers-Danlos syndrome, musculocontractural type 2

Similar variants

DSE p.Trp948Ter Uncertain significance ★ same residue
DSE c.416+1G>A Likely pathogenic ★★ same condition
DSE p.Ala122Thr Uncertain significance ★★ same condition
DSE p.Ala135Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala408Thr Uncertain significance ★★ ⚠ same condition
DSE p.Ala54Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala584Val Uncertain significance ★★ ⚠ same condition
DSE p.Ala688Val 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/dse-p-trp948arg (accessed [today's date]).

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