Is CSMD3 p.Leu30= (c.88C>T) pathogenic?

CSMD3 p.Leu30= (c.88C>T) is classified Benign in CSMD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-06). Rare (popmax 0.902%, afr); Associated with CSMD3-related disorder.

What condition is associated with CSMD3 p.Leu30= (c.88C>T)?

CSMD3 p.Leu30= (c.88C>T) is associated with CSMD3-related disorder (ClinVar).

How common is CSMD3 p.Leu30= (c.88C>T) in the general population?

CSMD3 p.Leu30= (c.88C>T) is rare (popmax 0.902%, afr) (gnomAD).

CSMD3 p.Leu30=

c.88C>T · rs113405539 · VCV3045912

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.902%, 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 7.5	GERP 0.41, phastCons 1
Overall
CADD	10.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.902% African / African-American · 677/75,026 alleles

Filtering AF 0.846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.824%

Overall 0.0466% 752/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.902%	111
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Admixed American	0.0283%	3,531
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,357
European (non-Finnish)	0.00127%	78,666

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.Leu30=
Coding: c.88C>T
MANE Select: NM_198123
dbSNP: rs113405539
Type: single nucleotide variant
Location: chr8:113436767 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)

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-leu30 (accessed [today's date]).

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