Is DSE p.Cys18Phe (c.53G>T) pathogenic?

DSE p.Cys18Phe (c.53G>T) is classified Benign/Likely benign in DSE (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0793); Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Ehlers-Danlos syndrome.

What condition is associated with DSE p.Cys18Phe (c.53G>T)?

DSE p.Cys18Phe (c.53G>T) is associated with Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, musculocontractural type 2 (ClinVar).

What do computational predictors say about DSE p.Cys18Phe (c.53G>T)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

DSE p.Cys18Phe

Q: How common is DSE p.Cys18Phe (c.53G>T) in the general population?

DSE p.Cys18Phe (c.53G>T) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.53G>T · rs76186865 · VCV387336

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ehlers-Danlos syndrome

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -6.79	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 4.3	phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 117 bp · p 0.73 · regional, not allelic
Overall
CADD	20.5	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 10.1% African / African-American · 7,563/74,978 alleles

Filtering AF 9.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.82%

Overall 0.621% 10,028/1,613,958 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Ashkenazi Jewishnot grpmax-eligible	1.94%	51
Middle Eastern	0.94%	106
Remaining individualsnot grpmax-eligible	0.912%	110
Admixed American	0.79%	127
European (non-Finnish)	0.0644%	1,553
South Asian	0.0318%	3,140

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.Cys18Phe
Coding: c.53G>T
MANE Select: NM_013352
dbSNP: rs76186865
Type: single nucleotide variant
Location: chr6:116399303 (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

Ehlers-Danlos syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ehlers-Danlos syndrome, musculocontractural type 2

Similar variants

DSE p.Cys18Tyr 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-cys18phe (accessed [today's date]).

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