Is CSDC2 p.Arg55Thr (c.164G>C) pathogenic?

CSDC2 p.Arg55Thr (c.164G>C) is classified Uncertain significance in CSDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely pathogenic (0.9998); Very rare (popmax 9.68e-05%, nfe).

How common is CSDC2 p.Arg55Thr (c.164G>C) in the general population?

CSDC2 p.Arg55Thr (c.164G>C) is very rare (popmax 9.68e-05%, nfe) (gnomAD).

What do computational predictors say about CSDC2 p.Arg55Thr (c.164G>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

CSDC2 p.Arg55Thr

c.164G>C · rs762132125 · VCV2330829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 9.68e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 5% in CSDC2
REVEL	0.552	indeterminate
SaProt	LLR -14.62	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 2,926 bp · p 0.21 · regional, not allelic
Overall
CADD	30.0	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 9.68e-05% European (non-Finnish) · 1/1,033,488 alleles

Overall 7.52e-05% 1/1,329,308 alleles · very rare exomes 1/1,176,974 · genomes 0/152,334 · joint denominator

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.Arg55Thr
Coding: c.164G>C
MANE Select: NM_014460
dbSNP: rs762132125
Type: single nucleotide variant
Location: chr22:41572129 (GRCh38)
Gene constraint: LOEUF 1.123 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.82
Residue 55: 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.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-arg55thr (accessed [today's date]).

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