Is CSDC2 p.Glu30Lys (c.88G>A) pathogenic?

CSDC2 p.Glu30Lys (c.88G>A) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.3545); Ultra-rare (popmax 0.0799%, afr).

How common is CSDC2 p.Glu30Lys (c.88G>A) in the general population?

CSDC2 p.Glu30Lys (c.88G>A) is ultra-rare (popmax 0.0799%, afr) (gnomAD).

What do computational predictors say about CSDC2 p.Glu30Lys (c.88G>A)?

AlphaMissense predicts ambiguous (score 0.3545) — an in-silico prediction, not a clinical call.

CSDC2 p.Glu30Lys

c.88G>A · rs561987799 · VCV2396430

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3545 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0799%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3545	ambiguous
REVEL	0.183	benign-leaning
SaProt	LLR -6.15	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.64 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 0.62, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	25.6	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 0.0799% African / African-American · 53/66,324 alleles

Filtering AF 0.0627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0565%

Overall 0.00712% 97/1,362,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0799%	1,251
Admixed American	0.0239%	4,191
Remaining individualsnot grpmax-eligible	0.0215%	4,656
Middle Eastern	0.0191%	5,224
European (non-Finnish)	0.00246%	40,596

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.Glu30Lys
Coding: c.88G>A
MANE Select: NM_014460
dbSNP: rs561987799
Type: single nucleotide variant
Location: chr22:41572053 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 30: 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.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.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-glu30lys (accessed [today's date]).

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