Is CSDC2 p.Arg43Gln (c.128G>A) pathogenic?

CSDC2 p.Arg43Gln (c.128G>A) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely benign (0.0879); Ultra-rare (popmax 0.0429%, eas).

How common is CSDC2 p.Arg43Gln (c.128G>A) in the general population?

CSDC2 p.Arg43Gln (c.128G>A) is ultra-rare (popmax 0.0429%, eas) (gnomAD).

What do computational predictors say about CSDC2 p.Arg43Gln (c.128G>A)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

CSDC2 p.Arg43Gln

c.128G>A · rs374172494 · VCV2354858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0429%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.55, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	23.5	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 0.0429% East Asian · 15/34,930 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.0053% 72/1,358,340 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0748%	1,336
East Asiangrpmax	0.0429%	2,329
Admixed American	0.0212%	4,707
Middle Eastern	0.0196%	5,098
European (non-Finnish)	0.00114%	87,579

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: CSDC2
Protein: p.Arg43Gln
Coding: c.128G>A
MANE Select: NM_014460
dbSNP: rs374172494
Type: single nucleotide variant
Location: chr22:41572093 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 43: the 'disordered' region

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

Similar variants

CSDC2 p.Arg43Trp Uncertain significance ★ ⚠ same residue
CSDC2 p.Arg33Ser Uncertain significance ★ ⚠ same type
CSDC2 p.Arg37Gln 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-arg43gln (accessed [today's date]).

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