Is CLMP p.Arg192Ter (c.574C>T) pathogenic?

CLMP p.Arg192Ter (c.574C>T) is classified Likely pathogenic in CLMP (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.000254%, nfe); Associated with congenital short bowel syndrome, autosomal recessive.

What condition is associated with CLMP p.Arg192Ter (c.574C>T)?

CLMP p.Arg192Ter (c.574C>T) is associated with congenital short bowel syndrome, autosomal recessive (ClinVar).

How common is CLMP p.Arg192Ter (c.574C>T) in the general population?

CLMP p.Arg192Ter (c.574C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

CLMP p.Arg192Ter

c.574C>T · rs1394600425 · VCV2500824

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

congenital short bowel syndrome, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 0.054, phastCons 0.99
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,946 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,738 alleles · very rare

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.Arg192Ter
Coding: c.574C>T
MANE Select: NM_024769
dbSNP: rs1394600425
Type: single nucleotide variant
Location: chr11:123083190 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.52
Residue 192: a disulfide bond; the ig-like c2-type 2 domain

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

Disease context

congenital short bowel syndrome, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLMP p.Arg222Ter Pathogenic ★★ same condition
CLMP c.28+1G>A Likely pathogenic ★ same condition
CLMP p.Arg82Ter Likely pathogenic ★ same condition
CLMP p.Leu8Ter Likely pathogenic ★ same condition
CLMP p.Arg274Gln Pathogenic ⚠ same condition
CLMP p.Val124Asp Pathogenic same condition
CLMP p.Glu77fs Pathogenic same condition
CLMP p.Asp55Asn Benign ★★ 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-arg192ter (accessed [today's date]).

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