Is CSTA p.Arg58Gln (c.173G>A) pathogenic?

CSTA p.Arg58Gln (c.173G>A) is classified Uncertain significance in CSTA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.0729); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with CSTA p.Arg58Gln (c.173G>A)?

CSTA p.Arg58Gln (c.173G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CSTA p.Arg58Gln (c.173G>A) in the general population?

CSTA p.Arg58Gln (c.173G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about CSTA p.Arg58Gln (c.173G>A)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

CSTA p.Arg58Gln

c.173G>A · VCV3497992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -5.82	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 -3.4	GERP -3.8
Regional constraint	o/e 1.04	unconstrained · MANE · 16 kb · p 0.65 · regional, not allelic
Overall
CADD	0.061	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 0.00534% African / African-American · 4/74,874 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000558% 9/1,613,638 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,718
East Asian	0.00223%	44,890
European (non-Finnish)	0.000339%	294,957

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.Arg58Gln
Coding: c.173G>A
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.Arg58Pro 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-arg58gln (accessed [today's date]).

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