Is DYM p.Ala327Asp (c.980C>A) pathogenic?

DYM p.Ala327Asp (c.980C>A) is classified Uncertain significance in DYM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-19). AlphaMissense: likely benign (0.2611); Ultra-rare (popmax 0.0458%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DYM p.Ala327Asp (c.980C>A)?

DYM p.Ala327Asp (c.980C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DYM p.Ala327Asp (c.980C>A) in the general population?

DYM p.Ala327Asp (c.980C>A) is ultra-rare (popmax 0.0458%, nfe) (gnomAD).

What do computational predictors say about DYM p.Ala327Asp (c.980C>A)?

AlphaMissense predicts likely benign (score 0.2611) — an in-silico prediction, not a clinical call.

DYM p.Ala327Asp

c.980C>A · rs147724274 · VCV326898

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2611 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0458%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2611	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 158 kb · p 0.51 · regional, not allelic
Overall
CADD	24.3	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 0.0458% European (non-Finnish) · 540/1,179,930 alleles

Filtering AF 0.0425% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0413%

Overall 0.0435% 702/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.105%	956
European (non-Finnish)grpmax	0.0458%	2,185
South Asian	0.045%	2,222
Admixed American	0.0433%	2,308
Remaining individualsnot grpmax-eligible	0.0288%	3,472
East Asian	0.0134%	7,475
African / African-American	0.004%	25,005
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala327Asp
Coding: c.980C>A
MANE Select: NM_001353214
dbSNP: rs147724274
Type: single nucleotide variant
Location: chr18:49282142 (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.Ala668Val Uncertain significance ★★ ⚠ same condition
DYM p.Arg475His Uncertain significance ★★ ⚠ same condition
DYM p.Arg673Gly 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-ala327asp (accessed [today's date]).

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