Is DYM p.Gln648Arg (c.1943A>G) pathogenic?

DYM p.Gln648Arg (c.1943A>G) is classified Conflicting classifications of pathogenicity in DYM (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.1016); Rare (popmax 0.974%, mid).

How common is DYM p.Gln648Arg (c.1943A>G) in the general population?

DYM p.Gln648Arg (c.1943A>G) is rare (popmax 0.974%, mid) (gnomAD).

What do computational predictors say about DYM p.Gln648Arg (c.1943A>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

DYM p.Gln648Arg

c.1943A>G · rs146000214 · VCV284211

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.974%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.601	indeterminate
SaProt	LLR -7.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 75 kb · p 0.42 · regional, not allelic
Overall
CADD	23.5	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 Q593R vs ClinVar Q648R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.974% Middle Eastern · 59/6,060 alleles

Filtering AF 0.775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.703%

Overall 0.0534% 862/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.974%	103
Ashkenazi Jewishnot grpmax-eligible	0.601%	166
Admixed American	0.115%	870
Remaining individualsnot grpmax-eligible	0.11%	906
South Asian	0.0505%	1,980
European (non-Finnish)	0.0362%	2,763
African / African-American	0.0187%	5,361

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.Gln648Arg
Coding: c.1943A>G
MANE Select: NM_001353214
dbSNP: rs146000214
Type: single nucleotide variant
Location: chr18:49097484 (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
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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-gln648arg (accessed [today's date]).

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