Is CLPB p.Ala492Ser (c.1474G>T) pathogenic?

CLPB p.Ala492Ser (c.1474G>T) is classified Likely benign in CLPB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1056); Rare (popmax 0.444%, afr); Associated with Inborn genetic diseases.

What condition is associated with CLPB p.Ala492Ser (c.1474G>T)?

CLPB p.Ala492Ser (c.1474G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLPB p.Ala492Ser (c.1474G>T) in the general population?

CLPB p.Ala492Ser (c.1474G>T) is rare (popmax 0.444%, afr) (gnomAD).

What do computational predictors say about CLPB p.Ala492Ser (c.1474G>T)?

AlphaMissense predicts likely benign (score 0.1056) — an in-silico prediction, not a clinical call.

CLPB p.Ala492Ser

c.1474G>T · rs145040658 · VCV784200

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1056 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.444%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1056	likely benign
REVEL	0.31	indeterminate
SaProt	LLR -8.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 2,250 bp · p 0.067 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A522S vs ClinVar A492S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.444% African / African-American · 333/75,056 alleles

Filtering AF 0.404% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.389%

Overall 0.022% 355/1,614,116 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.444%	225
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Admixed American	0.0117%	8,574
European (non-Finnish)	8.47e-05%	1,179,965

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.Ala492Ser
Coding: c.1474G>T
MANE Select: NM_001258392
dbSNP: rs145040658
Type: single nucleotide variant
Location: chr11:72295504 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 7 PDB
Residue 492: a β-strand

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.Ala492Gly Likely benign ★★ ⚠ same residue
CLPB p.Ala492= Likely benign ★★ same residue
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

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-ala492ser (accessed [today's date]).

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