Is CNGA3 p.Ala58Val (c.173C>T) pathogenic?

CNGA3 p.Ala58Val (c.173C>T) is classified Uncertain significance in CNGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-22). AlphaMissense: likely benign (0.0857); Very rare (popmax 8.47e-05%, nfe).

How common is CNGA3 p.Ala58Val (c.173C>T) in the general population?

CNGA3 p.Ala58Val (c.173C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CNGA3 p.Ala58Val (c.173C>T)?

AlphaMissense predicts likely benign (score 0.0857) — an in-silico prediction, not a clinical call.

CNGA3 p.Ala58Val

c.173C>T · rs1574375743 · VCV2129439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0857 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0857	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -6.67	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 3.9	GERP 1.7, phastCons 0.27
Regional constraint	o/e 1.15	unconstrained · MANE · 22 kb · p 0.013 · regional, not allelic
Overall
CADD	16.52	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 8.47e-05% European (non-Finnish) · 1/1,179,968 alleles

Overall 6.85e-05% 1/1,460,620 alleles · very rare

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: CNGA3
Protein: p.Ala58Val
Coding: c.173C>T
MANE Select: NM_001298
dbSNP: rs1574375743
Type: single nucleotide variant
Location: chr2:98377758 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB

Full CNGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNGA3 p.Ala58Thr Uncertain significance ★ same residue
CNGA3 c.216-1G>A Likely pathogenic ★★ same type
CNGA3 c.396-11C>G Pathogenic/Likely pathogenic ★★ same type
CNGA3 c.450-1G>A Pathogenic ★★ same type
CNGA3 p.Ala262Pro Likely pathogenic ★★ ⚠ same type
CNGA3 p.Ala318Thr Pathogenic ★★ same type
CNGA3 p.Ala469Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
CNGA3 p.Arg129Ter Pathogenic ★★ 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/cnga3-p-ala58val (accessed [today's date]).

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