Is CSMD1 p.Ser3074= (c.9222C>T) pathogenic?

CSMD1 p.Ser3074= (c.9222C>T) is classified Likely benign in CSMD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Very rare (popmax 0.00168%, amr); Associated with CSMD1-related disorder.

What condition is associated with CSMD1 p.Ser3074= (c.9222C>T)?

CSMD1 p.Ser3074= (c.9222C>T) is associated with CSMD1-related disorder (ClinVar).

How common is CSMD1 p.Ser3074= (c.9222C>T) in the general population?

CSMD1 p.Ser3074= (c.9222C>T) is very rare (popmax 0.00168%, amr) (gnomAD).

CSMD1 p.Ser3074=

c.9222C>T · VCV3351876

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Conditions

CSMD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.019	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.9
Overall
CADD	0.027	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,514 alleles

Filtering AF 0.000616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000475%

Overall 0.00087% 14/1,608,756 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,514
European (non-Finnish)	0.0011%	90,581

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.Ser3074=
Coding: c.9222C>T
MANE Select: NM_033225
Type: single nucleotide variant
Location: chr8:2965833 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 3074: a disulfide bond; the sushi 24 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-ser3074 (accessed [today's date]).

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