Is CSMD3 p.Gly838= (c.2514A>G) pathogenic?

CSMD3 p.Gly838= (c.2514A>G) is classified Likely benign in CSMD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-25). Rare (popmax 0.576%, mid); Associated with CSMD3-related disorder.

What condition is associated with CSMD3 p.Gly838= (c.2514A>G)?

CSMD3 p.Gly838= (c.2514A>G) is associated with CSMD3-related disorder (ClinVar).

How common is CSMD3 p.Gly838= (c.2514A>G) in the general population?

CSMD3 p.Gly838= (c.2514A>G) is rare (popmax 0.576%, mid) (gnomAD).

CSMD3 p.Gly838=

c.2514A>G · rs746135818 · VCV3057640

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.576%, mid)

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 0.7	GERP -2, phastCons 1
Overall
CADD	8.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.576% Middle Eastern · 35/6,072 alleles

Filtering AF 0.426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.374%

Overall 0.00564% 91/1,613,344 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.576%	173
Remaining individualsnot grpmax-eligible	0.0064%	15,615
South Asian	0.00549%	18,216
European (non-Finnish)	0.00373%	26,806
Admixed American	0.00333%	29,996
African / African-American	0.00133%	74,910

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.Gly838=
Coding: c.2514A>G
MANE Select: NM_198123
dbSNP: rs746135818
Type: single nucleotide variant
Location: chr8:112682605 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)
Residue 838: a disulfide bond; the sushi 4 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-gly838 (accessed [today's date]).

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