Is CLMP p.Val31Phe (c.91G>T) pathogenic?

CLMP p.Val31Phe (c.91G>T) is classified Uncertain significance in CLMP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely pathogenic (0.7939); Very rare (popmax 0.00224%, eas); Associated with Inborn genetic diseases.

What condition is associated with CLMP p.Val31Phe (c.91G>T)?

CLMP p.Val31Phe (c.91G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLMP p.Val31Phe (c.91G>T) in the general population?

CLMP p.Val31Phe (c.91G>T) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CLMP p.Val31Phe (c.91G>T)?

AlphaMissense predicts likely pathogenic (score 0.7939) — an in-silico prediction, not a clinical call.

CLMP p.Val31Phe

c.91G>T · rs140007158 · VCV2466661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7939 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7939	likely pathogenic
REVEL	0.762	pathogenic-leaning
SaProt	LLR -12.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 121 kb · p 0.032 · regional, not allelic
Overall
CADD	27.3	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 0.00224% East Asian · 1/44,606 alleles

Filtering AF 0.000543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00106% 17/1,609,918 alleles · very rare exomes 15/1,457,758 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,606
South Asian	0.00222%	45,093
Admixed American	0.00169%	59,344
Remaining individualsnot grpmax-eligible	0.00161%	62,294
European (non-Finnish)	0.00102%	98,186

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.Val31Phe
Coding: c.91G>T
MANE Select: NM_024769
dbSNP: rs140007158
Type: single nucleotide variant
Location: chr11:123097890 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.52
Residue 31: the ig-like c2-type 1 domain

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-val31phe (accessed [today's date]).

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