Is CSMD1 p.Ala2201Pro (c.6601G>C) pathogenic?

CSMD1 p.Ala2201Pro (c.6601G>C) is classified Uncertain significance in CSMD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely pathogenic (0.9841); Absent from gnomAD v4.1; Associated with CSMD1-related disorder.

What condition is associated with CSMD1 p.Ala2201Pro (c.6601G>C)?

CSMD1 p.Ala2201Pro (c.6601G>C) is associated with CSMD1-related disorder (ClinVar).

How common is CSMD1 p.Ala2201Pro (c.6601G>C) in the general population?

CSMD1 p.Ala2201Pro (c.6601G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSMD1 p.Ala2201Pro (c.6601G>C)?

AlphaMissense predicts likely pathogenic (score 0.9841) — an in-silico prediction, not a clinical call.

CSMD1 p.Ala2201Pro

c.6601G>C · VCV3348714

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

CSMD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9841	likely pathogenic · top 8% in CSMD1
REVEL	0.278	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP 0.86, phastCons 0.071
Regional constraint	o/e 1.53	unconstrained · MANE · 2,056 kb · p 5.8e-277 · regional, not allelic
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSMD1
Protein: p.Ala2201Pro
Coding: c.6601G>C
MANE Select: NM_033225
Type: single nucleotide variant
Location: chr8:3110165 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 2201: the cub 13 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-ala2201pro (accessed [today's date]).

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