Is CLMP p.Ser289Phe (c.866C>T) pathogenic?

CLMP p.Ser289Phe (c.866C>T) is classified Uncertain significance in CLMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.3164); Ultra-rare (popmax 0.0134%, amr); Associated with Inborn genetic diseases.

What condition is associated with CLMP p.Ser289Phe (c.866C>T)?

CLMP p.Ser289Phe (c.866C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLMP p.Ser289Phe (c.866C>T) in the general population?

CLMP p.Ser289Phe (c.866C>T) is ultra-rare (popmax 0.0134%, amr) (gnomAD).

What do computational predictors say about CLMP p.Ser289Phe (c.866C>T)?

AlphaMissense predicts likely benign (score 0.3164) — an in-silico prediction, not a clinical call.

CLMP p.Ser289Phe

c.866C>T · rs151226212 · VCV2591266

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3164 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3164	likely benign
REVEL	0.565	indeterminate
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 121 kb · p 0.032 · regional, not allelic
Overall
CADD	31.0	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 0.0134% Admixed American · 8/59,486 alleles

Filtering AF 0.00666% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00273% 44/1,611,478 alleles · ultra-rare exomes 37/1,459,256 · genomes 7/152,222 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0134%	7,436
Remaining individualsnot grpmax-eligible	0.00802%	12,465
European (non-Finnish)	0.00263%	38,027

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.Ser289Phe
Coding: c.866C>T
MANE Select: NM_024769
dbSNP: rs151226212
Type: single nucleotide variant
Location: chr11:123073730 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.52
Residue 289: the 'disordered' region

Full CLMP 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

CLMP p.Ala237Thr Uncertain significance ★ ⚠ same condition
CLMP p.Ala243Val Uncertain significance ★ ⚠ same condition
CLMP p.Ala279Thr Uncertain significance ★ ⚠ same condition
CLMP p.Ala311Val Uncertain significance ★ ⚠ same condition
CLMP p.Arg118His Uncertain significance ★ ⚠ same condition
CLMP p.Arg168Gln Uncertain significance ★ ⚠ same condition
CLMP p.Arg283His Uncertain significance ★ ⚠ same condition
CLMP p.Arg295Trp 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/clmp-p-ser289phe (accessed [today's date]).

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