Is CSMD3 p.Ala1760= (c.5280G>A) pathogenic?

CSMD3 p.Ala1760= (c.5280G>A) is classified Benign in CSMD3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-09). Common (popmax 10.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with CSMD3-related disorder.

What condition is associated with CSMD3 p.Ala1760= (c.5280G>A)?

CSMD3 p.Ala1760= (c.5280G>A) is associated with CSMD3-related disorder (ClinVar).

CSMD3 p.Ala1760=

Q: How common is CSMD3 p.Ala1760= (c.5280G>A) in the general population?

CSMD3 p.Ala1760= (c.5280G>A) is common (popmax 10.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5280G>A · rs12155677 · VCV3055693

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 10.7%, mid) — too common for a highly-penetrant pathogenic allele

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 0.011	GERP -2.7, phastCons 0.91
Overall
CADD	10.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.7% Middle Eastern · 643/6,010 alleles

Filtering AF 10% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.74%

Overall 7.48% 118,285/1,581,954 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	10.7%	9
Ashkenazi Jewishnot grpmax-eligible	8.78%	11
European (non-Finnish)	8.51%	12
Remaining individualsnot grpmax-eligible	6.92%	14
South Asian	6.21%	16
Admixed American	5.15%	19
Amishnot grpmax-eligible	5.05%	20
Finnishnot grpmax-eligible	4.57%	22
African / African-American	1.58%	63
East Asian	0.0224%	4,466

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.Ala1760=
Coding: c.5280G>A
MANE Select: NM_198123
dbSNP: rs12155677
Type: single nucleotide variant
Location: chr8:112472706 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)
Residue 1760: the sushi 9 domain

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

Disease context

CSMD3-related disorder

Similar variants

CSMD3 p.Ala1760Val Uncertain significance ★ ⚠ same residue
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

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-ala1760 (accessed [today's date]).

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