Is CSMD1 p.Ser87= (c.261A>G) pathogenic?

CSMD1 p.Ser87= (c.261A>G) is classified Benign in CSMD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-05). Common (popmax 6.25%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with CSMD1-related disorder.

What condition is associated with CSMD1 p.Ser87= (c.261A>G)?

CSMD1 p.Ser87= (c.261A>G) is associated with CSMD1-related disorder (ClinVar).

CSMD1 p.Ser87=

Q: How common is CSMD1 p.Ser87= (c.261A>G) in the general population?

CSMD1 p.Ser87= (c.261A>G) is common (popmax 6.25%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.261A>G · rs17417724 · VCV3037655

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 6.25%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

CSMD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.25% European (non-Finnish) · 73,770/1,179,712 alleles

Filtering AF 6.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.2%

Overall 5.5% 88,811/1,613,820 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	6.97%	14
European (non-Finnish)grpmax	6.25%	16
Amishnot grpmax-eligible	5.92%	17
Remaining individualsnot grpmax-eligible	4.95%	20
South Asian	4.68%	21
Finnishnot grpmax-eligible	4.65%	22
Middle Eastern	4.26%	23
Admixed American	2.74%	37
African / African-American	0.921%	109
East Asian	0.0134%	7,479

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser87=
Coding: c.261A>G
MANE Select: NM_033225
dbSNP: rs17417724
Type: single nucleotide variant
Location: chr8:4637383 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 87: the cub 1 domain

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

Disease context

CSMD1-related disorder

Similar variants

CSMD1 p.Ala1296Val Uncertain significance ★★ ⚠ same condition
CSMD1 p.Asp908Ala Uncertain significance ★★ ⚠ same condition
CSMD1 p.Gln308Leu Uncertain significance ★★ ⚠ same condition
CSMD1 p.Lys1718Asn Uncertain significance ★★ ⚠ same condition
CSMD1 p.Ser319Ter Pathogenic ★ same condition
CSMD1 c.10314+1G>A Uncertain significance ★ same condition
CSMD1 c.1344+31812G>A Uncertain significance ★ same condition
CSMD1 p.Ala1706Gly 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/csmd1-p-ser87 (accessed [today's date]).

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