Is DYM p.Leu573= (c.1717C>T) pathogenic?

DYM p.Leu573= (c.1717C>T) is classified Benign/Likely benign in DYM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.248%, mid).

How common is DYM p.Leu573= (c.1717C>T) in the general population?

DYM p.Leu573= (c.1717C>T) is rare (popmax 0.248%, mid) (gnomAD).

DYM p.Leu573=

c.1717C>T · rs145279594 · VCV283838

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.248%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP 6.4	GERP 0.91, phastCons 1
Overall
CADD	7.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% Middle Eastern · 15/6,054 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.201%

Overall 0.186% 3,000/1,610,362 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.249%	402
Middle Easterngrpmax	0.248%	404
Ashkenazi Jewishnot grpmax-eligible	0.247%	404
European (non-Finnish)	0.211%	474
Remaining individualsnot grpmax-eligible	0.207%	483
Admixed American	0.195%	512
African / African-American	0.0307%	3,257

Finnish 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: DYM
Protein: p.Leu573=
Coding: c.1717C>T
MANE Select: NM_001353214
dbSNP: rs145279594
Type: single nucleotide variant
Location: chr18:49163696 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.91

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

Similar variants

DYM c.1728+2T>C Pathogenic/Likely pathogenic ★★ same type
DYM c.947-2A>G Pathogenic/Likely pathogenic ★★ same type
DYM p.Arg204Ter Pathogenic ★★ same type
DYM p.Arg428Ter Pathogenic/Likely pathogenic ★★ same type
DYM p.Arg588Ter Pathogenic ★★ same type
DYM p.Arg70Ter Pathogenic/Likely pathogenic ★★ same type
DYM p.Gln306Ter Pathogenic/Likely pathogenic ★★ same type
DYM p.Glu87Lys Pathogenic ★★ 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/dym-p-leu573 (accessed [today's date]).

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