Is CSDC2 p.Arg37Gln (c.110G>A) pathogenic?

CSDC2 p.Arg37Gln (c.110G>A) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.1066); Ultra-rare (popmax 0.0193%, mid).

How common is CSDC2 p.Arg37Gln (c.110G>A) in the general population?

CSDC2 p.Arg37Gln (c.110G>A) is ultra-rare (popmax 0.0193%, mid) (gnomAD).

What do computational predictors say about CSDC2 p.Arg37Gln (c.110G>A)?

AlphaMissense predicts likely benign (score 0.1066) — an in-silico prediction, not a clinical call.

CSDC2 p.Arg37Gln

c.110G>A · VCV4656947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1066 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1066	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -6.83	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 9.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	25.5	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 0.0193% Middle Eastern · 1/5,174 alleles

Filtering AF 0.0029% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00189%

Overall 0.0022% 30/1,361,224 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0193%	5,174
South Asian	0.00826%	12,113
African / African-American	0.00752%	13,298
Admixed American	0.00374%	26,746
Remaining individualsnot grpmax-eligible	0.00196%	51,084
Finnishnot grpmax-eligible	0.00183%	54,746
European (non-Finnish)	0.00161%	61,946

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.Arg37Gln
Coding: c.110G>A
MANE Select: NM_014460
Type: single nucleotide variant
Location: chr22:41572075 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 37: the 'disordered' region

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

Similar variants

CSDC2 p.Arg33Ser 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-arg37gln (accessed [today's date]).

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