Is CLPS p.Ala50= (c.150G>A) pathogenic?

CLPS p.Ala50= (c.150G>A) is classified Benign in CLPS (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-27). Common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele.

CLPS p.Ala50=

Q: How common is CLPS p.Ala50= (c.150G>A) in the general population?

CLPS p.Ala50= (c.150G>A) is common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.150G>A · rs113528670 · VCV780119

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -3.1
Overall
CADD	1.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.54% African / African-American · 4,084/73,704 alleles

Filtering AF 5.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.34%

Overall 0.399% 6,428/1,610,678 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.54%	18
East Asian	2.85%	35
Remaining individualsnot grpmax-eligible	0.693%	144
Middle Eastern	0.578%	173
Admixed American	0.501%	200
South Asian	0.126%	791
Finnishnot grpmax-eligible	0.0254%	3,943
European (non-Finnish)	0.0158%	6,310

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.Ala50=
Coding: c.150G>A
MANE Select: NM_001832
dbSNP: rs113528670
Type: single nucleotide variant
Location: chr6:35795788 (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.Ala50Val Uncertain significance ★ ⚠ 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-ala50 (accessed [today's date]).

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