Is CLMP p.Ala243Val (c.728C>T) pathogenic?

CLMP p.Ala243Val (c.728C>T) is classified Uncertain significance in CLMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: likely benign (0.0964); Very rare (popmax 0.00602%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CLMP p.Ala243Val (c.728C>T)?

CLMP p.Ala243Val (c.728C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLMP p.Ala243Val (c.728C>T) in the general population?

CLMP p.Ala243Val (c.728C>T) is very rare (popmax 0.00602%, nfe) (gnomAD).

What do computational predictors say about CLMP p.Ala243Val (c.728C>T)?

AlphaMissense predicts likely benign (score 0.0964) — an in-silico prediction, not a clinical call.

CLMP p.Ala243Val

c.728C>T · rs369507357 · VCV2480285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0964 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00602%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0964	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -4.63	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 12	GERP 2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 121 kb · p 0.032 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00602% European (non-Finnish) · 71/1,180,014 alleles

Filtering AF 0.00486% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00447%

Overall 0.00446% 72/1,613,990 alleles · very rare exomes 65/1,461,850 · genomes 7/152,140 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00602%	16,620
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Ala243Val
Coding: c.728C>T
MANE Select: NM_024769
dbSNP: rs369507357
Type: single nucleotide variant
Location: chr11:123074795 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.52

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.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
CLMP p.Arg298Cys 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-ala243val (accessed [today's date]).

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