Is ASPDH p.Arg42Cys (c.124C>T) pathogenic?

ASPDH p.Arg42Cys (c.124C>T) is classified Uncertain significance in ASPDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: ambiguous (0.3636); Ultra-rare (popmax 0.0295%, eas).

How common is ASPDH p.Arg42Cys (c.124C>T) in the general population?

ASPDH p.Arg42Cys (c.124C>T) is ultra-rare (popmax 0.0295%, eas) (gnomAD).

What do computational predictors say about ASPDH p.Arg42Cys (c.124C>T)?

AlphaMissense predicts ambiguous (score 0.3636) — an in-silico prediction, not a clinical call.

ASPDH p.Arg42Cys

c.124C>T · VCV4155306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3636 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0295%, eas)

Computational evidence

Protein change
AlphaMissense	0.3636	ambiguous
REVEL	0.332	indeterminate
SaProt	LLR -13.12	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 2,090 bp · p 0.32 · 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 0.0295% East Asian · 12/40,712 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0133%

Overall 0.00162% 25/1,541,392 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0295%	3,393
South Asian	0.0121%	8,239
Remaining individualsnot grpmax-eligible	0.00168%	59,620
European (non-Finnish)	0.000175%	571,327

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: ASPDH
Protein: p.Arg42Cys
Coding: c.124C>T
MANE Select: NM_001114598
Type: single nucleotide variant
Location: chr19:50513345 (GRCh38)
Gene constraint: LOEUF 1.216 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.88

Full ASPDH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASPDH p.Arg42His Uncertain significance ★ ⚠ same residue
ASPDH p.Arg42Leu Uncertain significance ★ ⚠ same residue
ASPDH p.Ala120Thr Uncertain significance ★ ⚠ same type
ASPDH p.Ala127Thr Uncertain significance ★ ⚠ same type
ASPDH p.Ala139Glu Uncertain significance ★ ⚠ same type
ASPDH p.Ala187Val Uncertain significance ★ ⚠ same type
ASPDH p.Ala195Glu Uncertain significance ★ ⚠ same type
ASPDH p.Ala241Thr Uncertain significance ★ ⚠ 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/aspdh-p-arg42cys (accessed [today's date]).

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