Is CSMD1 p.Pro2488= (c.7464A>G) pathogenic?

CSMD1 p.Pro2488= (c.7464A>G) is classified Likely benign in CSMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Rare (popmax 0.182%, mid).

How common is CSMD1 p.Pro2488= (c.7464A>G) in the general population?

CSMD1 p.Pro2488= (c.7464A>G) is rare (popmax 0.182%, mid) (gnomAD).

CSMD1 p.Pro2488=

c.7464A>G · rs373936423 · VCV2658328

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.182%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.9
Overall
CADD	0.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.182% Middle Eastern · 10/5,492 alleles

Filtering AF 0.0988% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0751%

Overall 0.0603% 973/1,612,858 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.193%	519
Middle Easterngrpmax	0.182%	549
Finnishnot grpmax-eligible	0.139%	719
European (non-Finnish)	0.0618%	1,618
Remaining individualsnot grpmax-eligible	0.0561%	1,783
South Asian	0.0352%	2,845
Admixed American	0.0217%	4,615
African / African-American	0.0107%	9,371

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro2488=
Coding: c.7464A>G
MANE Select: NM_033225
dbSNP: rs373936423
Type: single nucleotide variant
Location: chr8:3087107 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 2488: a disulfide bond; the sushi 14 domain

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-pro2488 (accessed [today's date]).

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