Is CSDC2 p.Arg33Ser (c.99G>C) pathogenic?

CSDC2 p.Arg33Ser (c.99G>C) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: ambiguous (0.4036); Rare (popmax 0.149%, afr).

How common is CSDC2 p.Arg33Ser (c.99G>C) in the general population?

CSDC2 p.Arg33Ser (c.99G>C) is rare (popmax 0.149%, afr) (gnomAD).

What do computational predictors say about CSDC2 p.Arg33Ser (c.99G>C)?

AlphaMissense predicts ambiguous (score 0.4036) — an in-silico prediction, not a clinical call.

CSDC2 p.Arg33Ser

c.99G>C · rs142031815 · VCV3077957

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4036 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, afr)

Computational evidence

Protein change
AlphaMissense	0.4036	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -5.58	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -3.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	19.78	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 0.149% African / African-American · 99/66,452 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00822% 112/1,363,014 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.149%	671
Admixed American	0.0155%	6,451
Remaining individualsnot grpmax-eligible	0.0078%	12,817
Finnishnot grpmax-eligible	0.00182%	54,888
European (non-Finnish)	0.000379%	263,667

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.Arg33Ser
Coding: c.99G>C
MANE Select: NM_014460
dbSNP: rs142031815
Type: single nucleotide variant
Location: chr22:41572064 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 33: the 'disordered' region

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

Similar variants

CSDC2 p.Arg37Gln Uncertain significance ★ ⚠ same type
CSDC2 p.Arg43Gln Uncertain significance ★ ⚠ same type
CSDC2 p.Arg43Trp Uncertain significance ★ ⚠ same type
CSDC2 p.Arg55Thr Uncertain significance ★ ⚠ same type
CSDC2 p.Arg78Cys 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-arg33ser (accessed [today's date]).

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