Is CLPSL1 p.Cys61Gly (c.181T>G) pathogenic?

CLPSL1 p.Cys61Gly (c.181T>G) is classified Uncertain significance in CLPSL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.6781); Very rare (popmax 0.00133%, afr).

How common is CLPSL1 p.Cys61Gly (c.181T>G) in the general population?

CLPSL1 p.Cys61Gly (c.181T>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CLPSL1 p.Cys61Gly (c.181T>G)?

AlphaMissense predicts likely pathogenic (score 0.6781) — an in-silico prediction, not a clinical call.

CLPSL1 p.Cys61Gly

c.181T>G · VCV3267842

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6781 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6781	likely pathogenic
REVEL	0.181	moderately benign-leaning
SaProt	LLR -13.00	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61	GERP -1.2
Regional constraint	o/e 1.12	unconstrained · MANE · 6,896 bp · p 0.15 · regional, not allelic
Overall
CADD	17.12	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 0.00133% African / African-American · 1/75,078 alleles

Overall 6.86e-05% 1/1,457,538 alleles · very rare

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.Cys61Gly
Coding: c.181T>G
MANE Select: NM_001010886
Type: single nucleotide variant
Location: chr6:35787079 (GRCh38)
Gene constraint: LOEUF 1.867 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 61: 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.Arg87Trp Uncertain significance ★ ⚠ same type
CLPSL1 p.Cys45Ser 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-cys61gly (accessed [today's date]).

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