Is CNGA3 p.Ala71Pro (c.211G>C) pathogenic?

CNGA3 p.Ala71Pro (c.211G>C) is classified Uncertain significance in CNGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.0812); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CNGA3 p.Ala71Pro (c.211G>C)?

CNGA3 p.Ala71Pro (c.211G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CNGA3 p.Ala71Pro (c.211G>C) in the general population?

CNGA3 p.Ala71Pro (c.211G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CNGA3 p.Ala71Pro (c.211G>C)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

CNGA3 p.Ala71Pro

c.211G>C · rs61756692 · VCV3146446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -0.49, phastCons 0.057
Regional constraint	o/e 1.15	unconstrained · MANE · 22 kb · p 0.013 · regional, not allelic
Overall
CADD	11.7	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 0.000339% European (non-Finnish) · 4/1,179,004 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,457,504 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.Ala71Pro
Coding: c.211G>C
MANE Select: NM_001298
dbSNP: rs61756692
Type: single nucleotide variant
Location: chr2:98377796 (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

Disease context

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

Similar variants

CNGA3 p.Ala71Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
CNGA3 p.Ala71Val Uncertain significance ★ ⚠ same residue
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

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-ala71pro (accessed [today's date]).

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