Is CLP1 p.Ala138Val (c.413C>T) pathogenic?

CLP1 p.Ala138Val (c.413C>T) is classified Uncertain significance in CLP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely pathogenic (0.9743); Very rare (popmax 0.00223%, eas).

How common is CLP1 p.Ala138Val (c.413C>T) in the general population?

CLP1 p.Ala138Val (c.413C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CLP1 p.Ala138Val (c.413C>T)?

AlphaMissense predicts likely pathogenic (score 0.9743) — an in-silico prediction, not a clinical call.

CLP1 p.Ala138Val

c.413C>T · rs1290439063 · VCV1686575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9743 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9743	likely pathogenic
REVEL	0.339	indeterminate
SaProt	LLR -12.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 1,956 bp · p 8.6e-16 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,878 alleles

Overall 0.000137% 2/1,461,880 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	8.47e-05%	1,180,044

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: CLP1
Protein: p.Ala138Val
Coding: c.413C>T
MANE Select: NM_006831
dbSNP: rs1290439063
Type: single nucleotide variant
Location: chr11:57659889 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.95 · 2 PDB
Residue 138: an α-helix

Full CLP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLP1 p.Ala138Thr Uncertain significance ★ ⚠ same residue
CLP1 p.Ala138= Likely benign ★ same residue
CLP1 p.Arg140His Pathogenic/Likely pathogenic ★★ same type
CLP1 p.Arg116Gln Uncertain significance ★★ ⚠ same type
CLP1 p.Arg143Cys Uncertain significance ★★ ⚠ same type
CLP1 p.Arg288Cys Uncertain significance ★★ ⚠ same type
CLP1 p.Arg288His Uncertain significance ★★ ⚠ same type
CLP1 p.Asn95Ser 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/clp1-p-ala138val (accessed [today's date]).

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