Is CLMP p.Pro100Ser (c.298C>T) pathogenic?

CLMP p.Pro100Ser (c.298C>T) is classified Likely benign in CLMP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely benign (0.1674); Rare (popmax 0.144%, afr); Associated with CLMP-related disorder.

What condition is associated with CLMP p.Pro100Ser (c.298C>T)?

CLMP p.Pro100Ser (c.298C>T) is associated with CLMP-related disorder (ClinVar).

How common is CLMP p.Pro100Ser (c.298C>T) in the general population?

CLMP p.Pro100Ser (c.298C>T) is rare (popmax 0.144%, afr) (gnomAD).

What do computational predictors say about CLMP p.Pro100Ser (c.298C>T)?

AlphaMissense predicts likely benign (score 0.1674) — an in-silico prediction, not a clinical call.

CLMP p.Pro100Ser

c.298C>T · rs150466973 · VCV3058390

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1674 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CLMP-related disorder

Computational evidence

Protein change
AlphaMissense	0.1674	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 121 kb · p 0.032 · regional, not allelic
Overall
CADD	18.76	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 0.144% African / African-American · 108/75,052 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00799% 129/1,614,200 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.144%	695
Admixed American	0.025%	4,001
Remaining individualsnot grpmax-eligible	0.008%	12,502
South Asian	0.0011%	91,090

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: CLMP
Protein: p.Pro100Ser
Coding: c.298C>T
MANE Select: NM_024769
dbSNP: rs150466973
Type: single nucleotide variant
Location: chr11:123084602 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.52
Residue 100: a disulfide bond; the ig-like c2-type 1 domain

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

Disease context

CLMP-related disorder

Similar variants

CLMP p.Asp321= Likely benign same condition
CLMP p.Arg222Ter Pathogenic ★★ same type
CLMP p.Asp55Asn Benign ★★ same type
CLMP p.Gly337= Benign ★★ same type
CLMP p.Leu151= Benign ★★ same type
CLMP p.Ser296= Benign ★★ same type
CLMP c.28+1G>A Likely pathogenic ★ same type
CLMP p.Arg192Ter Likely pathogenic ★ 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/clmp-p-pro100ser (accessed [today's date]).

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