Is CSMD3 p.Pro1906= (c.5718A>G) pathogenic?

CSMD3 p.Pro1906= (c.5718A>G) is classified Likely benign in CSMD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-23). Rare (popmax 0.448%, afr); Associated with CSMD3-related disorder.

What condition is associated with CSMD3 p.Pro1906= (c.5718A>G)?

CSMD3 p.Pro1906= (c.5718A>G) is associated with CSMD3-related disorder (ClinVar).

How common is CSMD3 p.Pro1906= (c.5718A>G) in the general population?

CSMD3 p.Pro1906= (c.5718A>G) is rare (popmax 0.448%, afr) (gnomAD).

CSMD3 p.Pro1906=

c.5718A>G · rs148370497 · VCV3048103

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.448%, afr)

Conditions

CSMD3-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 2.9	GERP 0.62, phastCons 1
Overall
CADD	9.242	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.448% African / African-American · 336/75,006 alleles

Filtering AF 0.408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.393%

Overall 0.0222% 358/1,612,942 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.448%	223
Remaining individualsnot grpmax-eligible	0.0176%	5,676
Admixed American	0.0167%	5,996
European (non-Finnish)	8.48e-05%	1,179,116

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.Pro1906=
Coding: c.5718A>G
MANE Select: NM_198123
dbSNP: rs148370497
Type: single nucleotide variant
Location: chr8:112406615 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)
Residue 1906: a disulfide bond; the sushi 10 domain

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

Disease context

CSMD3-related disorder

Similar variants

CSMD3 p.Glu2761Val Uncertain significance ★★ same condition
CSMD3 p.Asp211His Uncertain significance ★ ⚠ same condition
CSMD3 c.7165+5G>A Uncertain significance same condition
CSMD3 p.Ala1895Val Uncertain significance ⚠ same condition
CSMD3 p.Asn1264Tyr Uncertain significance same condition
CSMD3 p.Asn2918Thr Uncertain significance same condition
CSMD3 p.Glu1266Ala Uncertain significance same condition
CSMD3 p.Met2992Ile 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/csmd3-p-pro1906 (accessed [today's date]).

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