Is DYM p.Pro303Ser (c.907C>T) pathogenic?

DYM p.Pro303Ser (c.907C>T) is classified Uncertain significance in DYM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.4366); Very rare (popmax 0.00703%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Pro303Ser (c.907C>T)?

DYM p.Pro303Ser (c.907C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Pro303Ser (c.907C>T) in the general population?

DYM p.Pro303Ser (c.907C>T) is very rare (popmax 0.00703%, nfe) (gnomAD).

What do computational predictors say about DYM p.Pro303Ser (c.907C>T)?

AlphaMissense predicts ambiguous (score 0.4366) — an in-silico prediction, not a clinical call.

DYM p.Pro303Ser

c.907C>T · rs200518242 · VCV2155691

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4366 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4366	ambiguous
REVEL	0.772	pathogenic-leaning
SaProt	LLR -10.58	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	26.9	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 0.00703% European (non-Finnish) · 83/1,180,000 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.00551% 89/1,614,126 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00703%	14,217
Finnishnot grpmax-eligible	0.00625%	16,010
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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.Pro303Ser
Coding: c.907C>T
MANE Select: NM_001353214
dbSNP: rs200518242
Type: single nucleotide variant
Location: chr18:49286473 (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-pro303ser (accessed [today's date]).

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