Is CSMD1 p.Asn40Ser (c.119A>G) pathogenic?

CSMD1 p.Asn40Ser (c.119A>G) is classified Uncertain significance in CSMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely benign (0.1074); Ultra-rare (popmax 0.0329%, mid).

How common is CSMD1 p.Asn40Ser (c.119A>G) in the general population?

CSMD1 p.Asn40Ser (c.119A>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CSMD1 p.Asn40Ser (c.119A>G)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

CSMD1 p.Asn40Ser

c.119A>G · rs200799805 · VCV2359262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.118	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.53	unconstrained · MANE · 2,056 kb · p 5.8e-277 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.00483% 78/1,613,676 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.00961%	10,411
East Asian	0.00891%	11,218
Admixed American	0.00667%	14,995
European (non-Finnish)	0.00492%	20,342
African / African-American	0.00267%	37,434
Finnishnot grpmax-eligible	0.00156%	63,984
South Asian	0.0011%	91,088

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.Asn40Ser
Coding: c.119A>G
MANE Select: NM_033225
dbSNP: rs200799805
Type: single nucleotide variant
Location: chr8:4637525 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 40: 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.Asn40Ile 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-asn40ser (accessed [today's date]).

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