Is ADPRS p.Ala195Ser (c.583G>T) pathogenic?

ADPRS p.Ala195Ser (c.583G>T) is classified Uncertain significance in ADPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: likely benign (0.1355); Ultra-rare (popmax 0.0204%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Ala195Ser (c.583G>T)?

ADPRS p.Ala195Ser (c.583G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Ala195Ser (c.583G>T) in the general population?

ADPRS p.Ala195Ser (c.583G>T) is ultra-rare (popmax 0.0204%, nfe) (gnomAD).

What do computational predictors say about ADPRS p.Ala195Ser (c.583G>T)?

AlphaMissense predicts likely benign (score 0.1355) — an in-silico prediction, not a clinical call.

ADPRS p.Ala195Ser

c.583G>T · rs146885889 · VCV3090443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1355 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0204%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1355	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.29	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0204% European (non-Finnish) · 241/1,179,934 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0174%

Overall 0.0164% 265/1,613,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0204%	4,896
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.012%	8,324
Admixed American	0.00667%	14,987
Finnishnot grpmax-eligible	0.00156%	64,030

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.Ala195Ser
Coding: c.583G>T
MANE Select: NM_017825
dbSNP: rs146885889
Type: single nucleotide variant
Location: chr1:36091976 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 195: a UniProt-annotated variant site (in condsias; no detectable protein in patient fibroblasts); 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.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-ala195ser (accessed [today's date]).

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