Is CLPSL1 p.Arg87Trp (c.259C>T) pathogenic?

CLPSL1 p.Arg87Trp (c.259C>T) is classified Uncertain significance in CLPSL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely benign (0.0916); Rare (popmax 0.181%, mid).

How common is CLPSL1 p.Arg87Trp (c.259C>T) in the general population?

CLPSL1 p.Arg87Trp (c.259C>T) is rare (popmax 0.181%, mid) (gnomAD).

What do computational predictors say about CLPSL1 p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely benign (score 0.0916) — an in-silico prediction, not a clinical call.

CLPSL1 p.Arg87Trp

c.259C>T · rs201083630 · VCV3145964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0916 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0916	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.53	GERP -1.8
Regional constraint	o/e 1.12	unconstrained · MANE · 6,896 bp · p 0.15 · regional, not allelic
Overall
CADD	14.94	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 0.181% Middle Eastern · 11/6,064 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.086%

Overall 0.0177% 284/1,606,962 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.181%	551
South Asian	0.11%	909
Remaining individualsnot grpmax-eligible	0.0643%	1,556
East Asian	0.0156%	6,403
European (non-Finnish)	0.00997%	10,032
African / African-American	0.00669%	14,958
Admixed American	0.00667%	15,000

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: CLPSL1
Protein: p.Arg87Trp
Coding: c.259C>T
MANE Select: NM_001010886
dbSNP: rs201083630
Type: single nucleotide variant
Location: chr6:35787903 (GRCh38)
Gene constraint: LOEUF 1.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 87: a disulfide bond

Full CLPSL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLPSL1 p.Ala116Val Uncertain significance ★ ⚠ same type
CLPSL1 p.Ala53Thr Uncertain significance ★ ⚠ same type
CLPSL1 p.Ala82Val Uncertain significance ★ ⚠ same type
CLPSL1 p.Arg106Cys Uncertain significance ★ ⚠ same type
CLPSL1 p.Arg112Met Uncertain significance ★ ⚠ same type
CLPSL1 p.Arg41Pro Uncertain significance ★ ⚠ same type
CLPSL1 p.Cys45Ser Uncertain significance ★ ⚠ same type
CLPSL1 p.Cys50Arg 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/clpsl1-p-arg87trp (accessed [today's date]).

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