Is CSMD1 p.Arg2003Lys (c.6008G>A) pathogenic?

CSMD1 p.Arg2003Lys (c.6008G>A) is classified Likely benign in CSMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely benign (0.0557); Very rare (popmax 0.000254%, nfe).

How common is CSMD1 p.Arg2003Lys (c.6008G>A) in the general population?

CSMD1 p.Arg2003Lys (c.6008G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CSMD1 p.Arg2003Lys (c.6008G>A)?

AlphaMissense predicts likely benign (score 0.0557) — an in-silico prediction, not a clinical call.

CSMD1 p.Arg2003Lys

c.6008G>A · VCV3497634

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0557	likely benign
REVEL	0.045	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.3	GERP -3.6
Regional constraint	o/e 1.53	unconstrained · MANE · 2,056 kb · p 5.8e-277 · regional, not allelic
Overall
CADD	0.309	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 0.000254% European (non-Finnish) · 3/1,178,904 alleles

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

Overall 0.000205% 3/1,460,414 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: CSMD1
Protein: p.Arg2003Lys
Coding: c.6008G>A
MANE Select: NM_033225
Type: single nucleotide variant
Location: chr8:3151420 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 2003: the cub 12 domain

Full CSMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSMD1 p.Ala1296Val Uncertain significance ★★ ⚠ same type
CSMD1 p.Asp908Ala Uncertain significance ★★ ⚠ same type
CSMD1 p.Asp927Asn Uncertain significance ★★ ⚠ same type
CSMD1 p.Gln308Leu Uncertain significance ★★ ⚠ same type
CSMD1 p.Glu1276Asp Uncertain significance ★★ ⚠ same type
CSMD1 p.Gly3156Arg Uncertain significance ★★ ⚠ same type
CSMD1 p.Ile1833Thr Uncertain significance ★★ ⚠ same type
CSMD1 p.Lys1718Asn Uncertain significance ★★ ⚠ 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/csmd1-p-arg2003lys (accessed [today's date]).

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