Is CSMD3 p.Pro1882Ser (c.5644C>T) pathogenic?

CSMD3 p.Pro1882Ser (c.5644C>T) is classified Uncertain significance in CSMD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.4944); Very rare (popmax 0.00223%, eas).

How common is CSMD3 p.Pro1882Ser (c.5644C>T) in the general population?

CSMD3 p.Pro1882Ser (c.5644C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CSMD3 p.Pro1882Ser (c.5644C>T)?

AlphaMissense predicts ambiguous (score 0.4944) — an in-silico prediction, not a clinical call.

CSMD3 p.Pro1882Ser

c.5644C>T · VCV4657188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4944 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
AlphaMissense	0.4944	ambiguous
REVEL	0.298	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 442 kb · p 0.031 · regional, not allelic
Overall
CADD	25.0	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 0.00223% East Asian · 1/44,750 alleles

Overall 0.000137% 2/1,458,912 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,750
African / African-American	0.00133%	74,962

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: CSMD3
Protein: p.Pro1882Ser
Coding: c.5644C>T
MANE Select: NM_198123
Type: single nucleotide variant
Location: chr8:112406689 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)
Residue 1882: a disulfide bond; the sushi 10 domain

Full CSMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSMD3 p.Glu2761Val Uncertain significance ★★ same type
CSMD3 p.Leu3027Phe Uncertain significance ★★ same type
CSMD3 c.4896-3C>T Benign ★★ same type
CSMD3 p.Arg1020His Benign ★★ same type
CSMD3 p.Arg1228Gln Likely benign ★★ same type
CSMD3 p.Arg687= Benign/Likely benign ★★ same type
CSMD3 p.Asp1025= Benign ★★ same type
CSMD3 p.Asp1473= Benign ★★ 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/csmd3-p-pro1882ser (accessed [today's date]).

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