Is CLPB p.Ala142Thr (c.424G>A) pathogenic?

CLPB p.Ala142Thr (c.424G>A) is classified Uncertain significance in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-05). AlphaMissense: likely benign (0.1972); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CLPB p.Ala142Thr (c.424G>A)?

CLPB p.Ala142Thr (c.424G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CLPB p.Ala142Thr (c.424G>A) in the general population?

CLPB p.Ala142Thr (c.424G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CLPB p.Ala142Thr (c.424G>A)?

AlphaMissense predicts likely benign (score 0.1972) — an in-silico prediction, not a clinical call.

CLPB p.Ala142Thr

c.424G>A · rs746090746 · VCV2270145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1972 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1972	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 117 kb · p 0.91 · regional, not allelic
Overall
CADD	26.8	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 0.00017% European (non-Finnish) · 2/1,179,860 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,112 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: CLPB
Protein: p.Ala142Thr
Coding: c.424G>A
MANE Select: NM_001258392
dbSNP: rs746090746
Type: single nucleotide variant
Location: chr11:72430343 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 7 PDB
Residue 142: an α-helix

Full CLPB 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

CLPB p.Ala120Gly Uncertain significance ★★ ⚠ same condition
CLPB p.Ala232Thr Uncertain significance ★★ ⚠ same condition
CLPB p.Ala85Val Uncertain significance ★★ ⚠ same condition
CLPB p.Arg231His Uncertain significance ★★ ⚠ same condition
CLPB p.Arg599Cys Uncertain significance ★★ ⚠ same condition
CLPB p.Arg620His Uncertain significance ★★ ⚠ same condition
CLPB p.Arg620Leu Uncertain significance ★★ ⚠ same condition
CLPB p.Arg644Cys 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/clpb-p-ala142thr (accessed [today's date]).

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