Is DYM p.Asp722Tyr (c.2164G>T) pathogenic?

DYM p.Asp722Tyr (c.2164G>T) is classified Uncertain significance in DYM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-01). AlphaMissense: ambiguous (0.3543); Ultra-rare (popmax 0.0312%, eas).

How common is DYM p.Asp722Tyr (c.2164G>T) in the general population?

DYM p.Asp722Tyr (c.2164G>T) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about DYM p.Asp722Tyr (c.2164G>T)?

AlphaMissense predicts ambiguous (score 0.3543) — an in-silico prediction, not a clinical call.

DYM p.Asp722Tyr

c.2164G>T · rs528865224 · VCV326888

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3543 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3543	ambiguous
REVEL	0.701	pathogenic-leaning
SaProt	LLR -7.31	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 75 kb · p 0.42 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D667Y vs ClinVar D722Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,890 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00223% 36/1,613,578 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,206
South Asian	0.00439%	22,763
Remaining individualsnot grpmax-eligible	0.0032%	31,228
European (non-Finnish)	0.00136%	73,752

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.Asp722Tyr
Coding: c.2164G>T
MANE Select: NM_001353214
dbSNP: rs528865224
Type: single nucleotide variant
Location: chr18:49044066 (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

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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-asp722tyr (accessed [today's date]).

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