Is CNGA3 p.Pro178Ser (c.532C>T) pathogenic?

CNGA3 p.Pro178Ser (c.532C>T) is classified Uncertain significance in CNGA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-15). AlphaMissense: ambiguous (0.4077); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CNGA3 p.Pro178Ser (c.532C>T)?

CNGA3 p.Pro178Ser (c.532C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CNGA3 p.Pro178Ser (c.532C>T) in the general population?

CNGA3 p.Pro178Ser (c.532C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about CNGA3 p.Pro178Ser (c.532C>T)?

AlphaMissense predicts ambiguous (score 0.4077) — an in-silico prediction, not a clinical call.

CNGA3 p.Pro178Ser

c.532C>T · rs370799365 · VCV1475944

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4077	ambiguous
REVEL	0.56	indeterminate
SaProt	LLR -4.74	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 22 kb · p 0.013 · regional, not allelic
Overall
CADD	20.2	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 0.00102% European (non-Finnish) · 12/1,180,018 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,382 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.Pro178Ser
Coding: c.532C>T
MANE Select: NM_001298
dbSNP: rs370799365
Type: single nucleotide variant
Location: chr2:98389740 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 178: an α-helix

Full CNGA3 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

CNGA3 p.Arg223Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
CNGA3 p.Ala28Thr Uncertain significance ★★ ⚠ same condition
CNGA3 p.Ala488Ser Uncertain significance ★★ ⚠ same condition
CNGA3 p.Ala597Thr Uncertain significance ★★ ⚠ same condition
CNGA3 p.Ala621Val Uncertain significance ★★ ⚠ same condition
CNGA3 p.Ala653Thr Uncertain significance ★★ ⚠ same condition
CNGA3 p.Arg129Thr Uncertain significance ★★ ⚠ same condition
CNGA3 p.Arg290Cys 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/cnga3-p-pro178ser (accessed [today's date]).

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