Is DYM p.Arg7Ser (c.21A>T) pathogenic?

DYM p.Arg7Ser (c.21A>T) is classified Uncertain significance in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1357); Ultra-rare (popmax 0.0201%, eas); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Arg7Ser (c.21A>T)?

DYM p.Arg7Ser (c.21A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Arg7Ser (c.21A>T) in the general population?

DYM p.Arg7Ser (c.21A>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about DYM p.Arg7Ser (c.21A>T)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

DYM p.Arg7Ser

c.21A>T · rs765630940 · VCV326909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -5.99	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 0.025	GERP 0.75, phastCons 0.14
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	10.03	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 0.0201% East Asian · 9/44,884 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00062% 10/1,613,806 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,987
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Arg7Ser
Coding: c.21A>T
MANE Select: NM_001353214
dbSNP: rs765630940
Type: single nucleotide variant
Location: chr18:49430374 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DYM p.Tyr132Ter Pathogenic/Likely pathogenic ★★ same condition
DYM p.Ala254Ser Uncertain significance ★★ ⚠ same condition
DYM p.Ala270Val Uncertain significance ★★ ⚠ same condition
DYM p.Ala300Val Uncertain significance ★★ ⚠ same condition
DYM p.Ala327Asp Uncertain significance ★★ ⚠ same condition
DYM p.Ala668Val Uncertain significance ★★ ⚠ same condition
DYM p.Arg475His Uncertain significance ★★ ⚠ same condition
DYM p.Arg673Gly 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/dym-p-arg7ser (accessed [today's date]).

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