Is CSDC2 p.Arg78Cys (c.232C>T) pathogenic?

CSDC2 p.Arg78Cys (c.232C>T) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.9845); Very rare (popmax 0.005%, amr).

How common is CSDC2 p.Arg78Cys (c.232C>T) in the general population?

CSDC2 p.Arg78Cys (c.232C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CSDC2 p.Arg78Cys (c.232C>T)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

CSDC2 p.Arg78Cys

c.232C>T · VCV4656945

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic
REVEL	0.543	indeterminate
SaProt	LLR -12.84	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.005% Admixed American · 3/60,012 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00109% 16/1,461,596 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,004
East Asian	0.00446%	22,440
European (non-Finnish)	0.000932%	107,268

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: CSDC2
Protein: p.Arg78Cys
Coding: c.232C>T
MANE Select: NM_014460
Type: single nucleotide variant
Location: chr22:41573710 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 78: the csd domain

Full CSDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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CSDC2 p.Arg43Trp Uncertain significance ★ ⚠ same type
CSDC2 p.Arg55Thr Uncertain significance ★ ⚠ same type
CSDC2 p.Asp111Gly Uncertain significance ★ ⚠ same type
CSDC2 p.Glu30Lys Uncertain significance ★ ⚠ same type
CSDC2 p.Glu88Ala 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/csdc2-p-arg78cys (accessed [today's date]).

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