Is DYM p.Arg673Gly (c.2017A>G) pathogenic?

DYM p.Arg673Gly (c.2017A>G) is classified Uncertain significance in DYM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.274); Ultra-rare (popmax 0.0409%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Arg673Gly (c.2017A>G)?

DYM p.Arg673Gly (c.2017A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Arg673Gly (c.2017A>G) in the general population?

DYM p.Arg673Gly (c.2017A>G) is ultra-rare (popmax 0.0409%, nfe) (gnomAD).

What do computational predictors say about DYM p.Arg673Gly (c.2017A>G)?

AlphaMissense predicts likely benign (score 0.274) — an in-silico prediction, not a clinical call.

DYM p.Arg673Gly

c.2017A>G · rs142608802 · VCV2176352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.274 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0409%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.274	likely benign
REVEL	0.623	indeterminate
SaProt	LLR -9.95	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 4.4	GERP 0.23, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 75 kb · p 0.42 · regional, not allelic
Overall
CADD	22.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R618G vs ClinVar R673G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0409% European (non-Finnish) · 483/1,179,874 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.0315% 508/1,613,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0409%	2,443
Remaining individualsnot grpmax-eligible	0.0208%	4,805
African / African-American	0.0133%	7,492
Admixed American	0.00167%	59,982
Finnishnot grpmax-eligible	0.00156%	64,024

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.Arg673Gly
Coding: c.2017A>G
MANE Select: NM_001353214
dbSNP: rs142608802
Type: single nucleotide variant
Location: chr18:49097410 (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.Asn282Ser 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-arg673gly (accessed [today's date]).

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