Is CLMP p.Arg69Cys (c.205C>T) pathogenic?

CLMP p.Arg69Cys (c.205C>T) is classified Uncertain significance in CLMP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). AlphaMissense: likely benign (0.1879); Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with CLMP p.Arg69Cys (c.205C>T)?

CLMP p.Arg69Cys (c.205C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CLMP p.Arg69Cys (c.205C>T) in the general population?

CLMP p.Arg69Cys (c.205C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CLMP p.Arg69Cys (c.205C>T)?

AlphaMissense predicts likely benign (score 0.1879) — an in-silico prediction, not a clinical call.

CLMP p.Arg69Cys

c.205C>T · rs746453314 · VCV3145919

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1879	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -10.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 121 kb · p 0.032 · regional, not allelic
Overall
CADD	32.0	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 0.00329% South Asian · 3/91,052 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,613,950 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,351
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Arg69Cys
Coding: c.205C>T
MANE Select: NM_024769
dbSNP: rs746453314
Type: single nucleotide variant
Location: chr11:123084695 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.52
Residue 69: a UniProt-annotated variant site (in); 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-arg69cys (accessed [today's date]).

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