Is DYM p.Ile78Ser (c.233T>G) pathogenic?

DYM p.Ile78Ser (c.233T>G) is classified Uncertain significance in DYM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-04). AlphaMissense: ambiguous (0.5471); Very rare (popmax 0.00212%, nfe).

How common is DYM p.Ile78Ser (c.233T>G) in the general population?

DYM p.Ile78Ser (c.233T>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about DYM p.Ile78Ser (c.233T>G)?

AlphaMissense predicts ambiguous (score 0.5471) — an in-silico prediction, not a clinical call.

DYM p.Ile78Ser

c.233T>G · rs770135743 · VCV1377059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5471 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5471	ambiguous
REVEL	0.836	moderately pathogenic-leaning
SaProt	LLR -10.91	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.56	donor gain · deltas
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	33.0	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 0.00212% European (non-Finnish) · 25/1,179,550 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00171% 25/1,461,118 alleles · very rare

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.Ile78Ser
Coding: c.233T>G
MANE Select: NM_001353214
dbSNP: rs770135743
Type: single nucleotide variant
Location: chr18:49379719 (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-ile78ser (accessed [today's date]).

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