Is CSMD1 p.Asp908Ala (c.2723A>C) pathogenic?

CSMD1 p.Asp908Ala (c.2723A>C) is classified Uncertain significance in CSMD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-19). AlphaMissense: likely benign (0.0928); Very rare (popmax 0.00855%, amr); Associated with CSMD1-related disorder.

What condition is associated with CSMD1 p.Asp908Ala (c.2723A>C)?

CSMD1 p.Asp908Ala (c.2723A>C) is associated with CSMD1-related disorder (ClinVar).

How common is CSMD1 p.Asp908Ala (c.2723A>C) in the general population?

CSMD1 p.Asp908Ala (c.2723A>C) is very rare (popmax 0.00855%, amr) (gnomAD).

What do computational predictors say about CSMD1 p.Asp908Ala (c.2723A>C)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

CSMD1 p.Asp908Ala

c.2723A>C · VCV3836755

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00855%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

CSMD1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.149	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 3.2	GERP -0.58, phastCons 1
Regional constraint	o/e 1.53	unconstrained · MANE · 2,056 kb · p 5.8e-277 · regional, not allelic
Overall
CADD	22.9	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 0.00855% Admixed American · 5/58,468 alleles

Filtering AF 0.00332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.000414% 6/1,449,768 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00855%	11,694
European (non-Finnish)	8.52e-05%	1,174,200

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.Asp908Ala
Coding: c.2723A>C
MANE Select: NM_033225
Type: single nucleotide variant
Location: chr8:3387553 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Residue 908: a disulfide bond; the sushi 5 domain

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

Disease context

CSMD1-related disorder

Similar variants

CSMD1 p.Asp908Glu Uncertain significance ★ ⚠ same residue
CSMD1 p.Ala1296Val Uncertain significance ★★ ⚠ same condition
CSMD1 p.Gln308Leu Uncertain significance ★★ ⚠ same condition
CSMD1 p.Lys1718Asn Uncertain significance ★★ ⚠ same condition
CSMD1 p.Ser319Ter Pathogenic ★ same condition
CSMD1 c.10314+1G>A Uncertain significance ★ same condition
CSMD1 c.1344+31812G>A Uncertain significance ★ same condition
CSMD1 p.Ala1706Gly 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/csmd1-p-asp908ala (accessed [today's date]).

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