Is CSMD1 p.Glu44Lys (c.130G>A) pathogenic?

CSMD1 p.Glu44Lys (c.130G>A) is classified Uncertain significance in CSMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-05). AlphaMissense: ambiguous (0.4691); Ultra-rare (popmax 0.02%, amr).

How common is CSMD1 p.Glu44Lys (c.130G>A) in the general population?

CSMD1 p.Glu44Lys (c.130G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about CSMD1 p.Glu44Lys (c.130G>A)?

AlphaMissense predicts ambiguous (score 0.4691) — an in-silico prediction, not a clinical call.

CSMD1 p.Glu44Lys

c.130G>A · VCV3836735

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Computational evidence

Protein change
AlphaMissense	0.4691	ambiguous
REVEL	0.206	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.96, phastCons 1
Regional constraint	o/e 1.53	unconstrained · MANE · 2,056 kb · p 5.8e-277 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/59,984 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.000744% 12/1,613,750 alleles · ultra-rare

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.Glu44Lys
Coding: c.130G>A
MANE Select: NM_033225
Type: single nucleotide variant
Location: chr8:4637514 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 44: the cub 1 domain; a disulfide bond

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

Similar variants

CSMD1 p.Glu44Gln Uncertain significance ★ ⚠ same residue
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

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-glu44lys (accessed [today's date]).

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