Is CLPS p.Ala50Val (c.149C>T) pathogenic?

CLPS p.Ala50Val (c.149C>T) is classified Uncertain significance in CLPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). AlphaMissense: likely benign (0.0896); Ultra-rare (popmax 0.0693%, afr).

How common is CLPS p.Ala50Val (c.149C>T) in the general population?

CLPS p.Ala50Val (c.149C>T) is ultra-rare (popmax 0.0693%, afr) (gnomAD).

What do computational predictors say about CLPS p.Ala50Val (c.149C>T)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

CLPS p.Ala50Val

c.149C>T · VCV4003807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0693%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -5.20	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 -1.1	GERP -3.1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,139 bp · p 0.89 · regional, not allelic
Overall
CADD	5.151	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 0.0693% African / African-American · 52/75,026 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0489%

Overall 0.00558% 90/1,613,176 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0693%	1,443
East Asian	0.0156%	6,410
Finnishnot grpmax-eligible	0.0111%	9,010
Admixed American	0.00666%	15,005
Remaining individualsnot grpmax-eligible	0.0064%	15,624
South Asian	0.0022%	45,541
European (non-Finnish)	0.00119%	84,288

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: CLPS
Protein: p.Ala50Val
Coding: c.149C>T
MANE Select: NM_001832
Type: single nucleotide variant
Location: chr6:35795789 (GRCh38)
Gene constraint: LOEUF 1.423 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.89
Residue 50: a disulfide bond

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

Similar variants

CLPS p.Ala50= Benign ★ same residue
CLPS p.Asn43Ile Uncertain significance ★ ⚠ same type
CLPS p.Cys80Arg Uncertain significance ★ ⚠ same type
CLPS p.Glu65Lys Uncertain significance ★ ⚠ same type
CLPS p.Glu81Asp Uncertain significance ★ ⚠ same type
CLPS p.Gly102Asp Uncertain significance ★ ⚠ same type
CLPS p.His47Gln Uncertain significance ★ ⚠ same type
CLPS p.Leu71Pro 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/clps-p-ala50val (accessed [today's date]).

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