Is CSMD1 p.Ala764= (c.2292G>T) pathogenic?

CSMD1 p.Ala764= (c.2292G>T) is classified Likely benign in CSMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-28). Ultra-rare (popmax 0.0964%, afr).

How common is CSMD1 p.Ala764= (c.2292G>T) in the general population?

CSMD1 p.Ala764= (c.2292G>T) is ultra-rare (popmax 0.0964%, afr) (gnomAD).

CSMD1 p.Ala764=

c.2292G>T · rs374326454 · VCV797376

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0964%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.12	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -4.1
Overall
CADD	0.029	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0964% African / African-American · 72/74,722 alleles

Filtering AF 0.0785% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0718%

Overall 0.00718% 115/1,602,754 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0964%	1,038
Admixed American	0.0325%	3,072
Remaining individualsnot grpmax-eligible	0.0193%	5,170
European (non-Finnish)	0.00102%	97,923

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: CSMD1
Protein: p.Ala764=
Coding: c.2292G>T
MANE Select: NM_033225
dbSNP: rs374326454
Type: single nucleotide variant
Location: chr8:3399504 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 764: the cub 5 domain; a disulfide bond

Full CSMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSMD1 p.Ala1296Val Uncertain significance ★★ ⚠ same type
CSMD1 p.Asp908Ala Uncertain significance ★★ ⚠ same type
CSMD1 p.Asp927Asn Uncertain significance ★★ ⚠ same type
CSMD1 p.Gln308Leu Uncertain significance ★★ ⚠ same type
CSMD1 p.Glu1276Asp Uncertain significance ★★ ⚠ same type
CSMD1 p.Gly3156Arg Uncertain significance ★★ ⚠ same type
CSMD1 p.Ile1833Thr Uncertain significance ★★ ⚠ same type
CSMD1 p.Lys1718Asn Uncertain significance ★★ ⚠ 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/csmd1-p-ala764 (accessed [today's date]).

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