Is DYM p.Ile167Thr (c.500T>C) pathogenic?

DYM p.Ile167Thr (c.500T>C) is classified Uncertain significance in DYM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-03). AlphaMissense: ambiguous (0.5187); Ultra-rare (popmax 0.029%, eas); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Ile167Thr (c.500T>C)?

DYM p.Ile167Thr (c.500T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Ile167Thr (c.500T>C) in the general population?

DYM p.Ile167Thr (c.500T>C) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about DYM p.Ile167Thr (c.500T>C)?

AlphaMissense predicts ambiguous (score 0.5187) — an in-silico prediction, not a clinical call.

DYM p.Ile167Thr

c.500T>C · rs75854087 · VCV1362456

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5187 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5187	ambiguous
REVEL	0.569	indeterminate
SaProt	LLR -7.34	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	23.4	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 0.029% East Asian · 13/44,794 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00162% 26/1,609,310 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,446
African / African-American	0.008%	12,494
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0016%	62,340
South Asian	0.0011%	90,916
European (non-Finnish)	0.000255%	392,198

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.Ile167Thr
Coding: c.500T>C
MANE Select: NM_001353214
dbSNP: rs75854087
Type: single nucleotide variant
Location: chr18:49333848 (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.Ile167Asn Benign/Likely benign ★★ ⚠ same residue
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

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-ile167thr (accessed [today's date]).

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