Is ADPRS p.Ala5Val (c.14C>T) pathogenic?

ADPRS p.Ala5Val (c.14C>T) is classified Likely benign in ADPRS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely benign (0.2952); Rare (popmax 0.129%, mid); Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Ala5Val (c.14C>T)?

ADPRS p.Ala5Val (c.14C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Ala5Val (c.14C>T) in the general population?

ADPRS p.Ala5Val (c.14C>T) is rare (popmax 0.129%, mid) (gnomAD).

What do computational predictors say about ADPRS p.Ala5Val (c.14C>T)?

AlphaMissense predicts likely benign (score 0.2952) — an in-silico prediction, not a clinical call.

ADPRS p.Ala5Val

c.14C>T · VCV4570958

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2952 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.129%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2952	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -9.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -1.8
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	6.578	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 0.129% Middle Eastern · 6/4,634 alleles

Filtering AF 0.0563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00688% 105/1,525,268 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.129%	772
Remaining individualsnot grpmax-eligible	0.00844%	11,850
European (non-Finnish)	0.00788%	12,683
Admixed American	0.004%	24,982
South Asian	0.0024%	41,703

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: ADPRS
Protein: p.Ala5Val
Coding: c.14C>T
MANE Select: NM_017825
Type: single nucleotide variant
Location: chr1:36088918 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB

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 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
ADPRS p.Ala42Val 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-ala5val (accessed [today's date]).

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