Is CSMD3 p.Asp211His (c.631G>C) pathogenic?

CSMD3 p.Asp211His (c.631G>C) is classified Uncertain significance in CSMD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely pathogenic (0.8917); Very rare (popmax 0.000932%, nfe); Associated with CSMD3-related disorder.

What condition is associated with CSMD3 p.Asp211His (c.631G>C)?

CSMD3 p.Asp211His (c.631G>C) is associated with CSMD3-related disorder (ClinVar).

How common is CSMD3 p.Asp211His (c.631G>C) in the general population?

CSMD3 p.Asp211His (c.631G>C) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about CSMD3 p.Asp211His (c.631G>C)?

AlphaMissense predicts likely pathogenic (score 0.8917) — an in-silico prediction, not a clinical call.

CSMD3 p.Asp211His

c.631G>C · rs777486805 · VCV2632328

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

CSMD3-related disorder

Computational evidence

Protein change
AlphaMissense	0.8917	likely pathogenic
REVEL	0.23	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 607 kb · p 0.37 · regional, not allelic
Overall
CADD	27.6	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 0.000932% European (non-Finnish) · 11/1,179,818 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000744% 12/1,613,738 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)grpmax	0.000932%	107,256

Remaining individuals 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: CSMD3
Protein: p.Asp211His
Coding: c.631G>C
MANE Select: NM_198123
dbSNP: rs777486805
Type: single nucleotide variant
Location: chr8:113173800 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.97 (gnomAD)
Residue 211: the sushi 1 domain; a disulfide bond

Full CSMD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CSMD3-related disorder

Similar variants

CSMD3 p.Glu2761Val Uncertain significance ★★ same condition
CSMD3 c.7165+5G>A Uncertain significance same condition
CSMD3 p.Ala1895Val Uncertain significance ⚠ same condition
CSMD3 p.Asn1264Tyr Uncertain significance same condition
CSMD3 p.Asn2918Thr Uncertain significance same condition
CSMD3 p.Glu1266Ala Uncertain significance same condition
CSMD3 p.Met2992Ile Uncertain significance ⚠ same condition
CSMD3 p.Pro1587Leu 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/csmd3-p-asp211his (accessed [today's date]).

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