Is CSTA p.Arg58Pro (c.173G>C) pathogenic?

CSTA p.Arg58Pro (c.173G>C) is classified Uncertain significance in CSTA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely pathogenic (0.6985); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CSTA p.Arg58Pro (c.173G>C)?

CSTA p.Arg58Pro (c.173G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CSTA p.Arg58Pro (c.173G>C) in the general population?

CSTA p.Arg58Pro (c.173G>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CSTA p.Arg58Pro (c.173G>C)?

AlphaMissense predicts likely pathogenic (score 0.6985) — an in-silico prediction, not a clinical call.

CSTA p.Arg58Pro

c.173G>C · VCV4235354

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6985 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6985	likely pathogenic
REVEL	0.237	benign-leaning
SaProt	LLR -11.01	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.4	GERP -3.8
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.65 · regional, not allelic
Overall
CADD	4.965	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 0.000678% European (non-Finnish) · 8/1,179,818 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,756 alleles · very rare exomes 8/1,461,562 · genomes 0/152,194 · 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: CSTA
Protein: p.Arg58Pro
Coding: c.173G>C
MANE Select: NM_005213
Type: single nucleotide variant
Location: chr3:122341443 (GRCh38)
Gene constraint: LOEUF 1.219 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 93.57 · 14 PDB
Residue 58: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSTA p.Arg58Gln Uncertain significance ★ ⚠ same residue
CSTA p.Arg58Ter Likely pathogenic ★★ same residue
CSTA p.Ala12Thr Uncertain significance ★ ⚠ same condition
CSTA p.Asp92Val Uncertain significance ★ ⚠ same condition
CSTA p.Gln17Arg Uncertain significance ★ ⚠ same condition
CSTA p.Gln42Arg Uncertain significance ★ ⚠ same condition
CSTA p.Glu94Lys Uncertain significance ★ ⚠ same condition
CSTA p.Lys30Asn Uncertain significance ★ ⚠ same condition

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/csta-p-arg58pro (accessed [today's date]).

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