Is ADPRS p.Ala42Val (c.125C>T) pathogenic?

ADPRS p.Ala42Val (c.125C>T) is classified Uncertain significance in ADPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: ambiguous (0.3636); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Ala42Val (c.125C>T)?

ADPRS p.Ala42Val (c.125C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Ala42Val (c.125C>T) in the general population?

ADPRS p.Ala42Val (c.125C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADPRS p.Ala42Val (c.125C>T)?

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

ADPRS p.Ala42Val

c.125C>T · rs1188484640 · VCV3090389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3636 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,473,914)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3636	ambiguous
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	24.0	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

No allele count reported in gnomAD v4.1 (AN 1,473,914). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ADPRS
Protein: p.Ala42Val
Coding: c.125C>T
MANE Select: NM_017825
dbSNP: rs1188484640
Type: single nucleotide variant
Location: chr1:36089029 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 42: an α-helix

Full ADPRS 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

ADPRS p.Ala94Asp Uncertain significance ★★ ⚠ same condition
ADPRS p.Ala5Val Likely benign ★★ same condition
ADPRS c.517-4C>G Uncertain significance ★ same condition
ADPRS p.Ala101Thr Uncertain significance ★ ⚠ same condition
ADPRS p.Ala14Pro Uncertain significance ★ ⚠ same condition
ADPRS p.Ala16Gly Uncertain significance ★ ⚠ same condition
ADPRS p.Ala191Thr Uncertain significance ★ same condition
ADPRS p.Ala195Ser 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/adprs-p-ala42val (accessed [today's date]).

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