Is CSMD2 p.Val1867Met (c.5599G>A) pathogenic?

CSMD2 p.Val1867Met (c.5599G>A) is classified Likely benign in CSMD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely benign (0.0763); Ultra-rare (popmax 0.0665%, nfe).

How common is CSMD2 p.Val1867Met (c.5599G>A) in the general population?

CSMD2 p.Val1867Met (c.5599G>A) is ultra-rare (popmax 0.0665%, nfe) (gnomAD).

What do computational predictors say about CSMD2 p.Val1867Met (c.5599G>A)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

CSMD2 p.Val1867Met

c.5599G>A · rs149848489 · VCV2368796

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0665%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.026	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 -0.64	GERP -4.6, phastCons 0.029
Regional constraint	o/e 0.78	unconstrained · MANE · 331 kb · p 5.5e-29 · regional, not allelic
Overall
CADD	13.94	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V1827M vs ClinVar V1867M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0665% European (non-Finnish) · 785/1,179,896 alleles

Filtering AF 0.0626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0611%

Overall 0.0511% 824/1,613,790 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0665%	1,503
Remaining individualsnot grpmax-eligible	0.0352%	2,840
African / African-American	0.0133%	7,492
Admixed American	0.01%	10,001
East Asian	0.00223%	44,876

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: CSMD2
Protein: p.Val1867Met
Coding: c.5599G>A
MANE Select: NM_001281956
dbSNP: rs149848489
Type: single nucleotide variant
Location: chr1:33624545 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Residue 1867: the cub 11 domain

Full CSMD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSMD2 p.Pro1506= Likely benign ★★ same type
CSMD2 p.Ser3015= Benign ★★ same type
CSMD2 c.404+2T>A Uncertain significance ★ same type
CSMD2 c.6344-398G>T Uncertain significance ★ same type
CSMD2 c.6344-422A>G Uncertain significance ★ same type
CSMD2 c.6344-423T>C Uncertain significance ★ same type
CSMD2 c.6344-429G>A Uncertain significance ★ same type
CSMD2 c.6344-435G>A 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/csmd2-p-val1867met (accessed [today's date]).

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