Is CNGA1 p.Gln415Pro (c.1244A>C) pathogenic?

CNGA1 p.Gln415Pro (c.1244A>C) is classified Uncertain significance in CNGA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-09-09). AlphaMissense: likely pathogenic (0.9697); Very rare (popmax 0.000678%, nfe).

How common is CNGA1 p.Gln415Pro (c.1244A>C) in the general population?

CNGA1 p.Gln415Pro (c.1244A>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CNGA1 p.Gln415Pro (c.1244A>C)?

AlphaMissense predicts likely pathogenic (score 0.9697) — an in-silico prediction, not a clinical call.

CNGA1 p.Gln415Pro

c.1244A>C · rs1381823986 · VCV1516487

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.9697	likely pathogenic
REVEL	0.865	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q419P vs ClinVar Q415P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,046 alleles

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

Overall 0.000496% 8/1,614,068 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: CNGA1
Protein: p.Gln415Pro
Coding: c.1244A>C
MANE Select: NM_001379270
dbSNP: rs1381823986
Type: single nucleotide variant
Location: chr4:47937238 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 415: the 'c-linker' region; an α-helix

Full CNGA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNGA1 c.107+1G>A Likely pathogenic ★★ same type
CNGA1 c.107+2T>G Likely pathogenic ★★ same type
CNGA1 c.545+2T>A Likely pathogenic ★★ same type
CNGA1 c.545+2T>C Likely pathogenic ★★ same type
CNGA1 c.546-1G>C Pathogenic/Likely pathogenic ★★ same type
CNGA1 p.Arg214Ter Pathogenic ★★ same type
CNGA1 p.Arg28Ter Pathogenic ★★ same type
CNGA1 p.Arg420Ter Pathogenic/Likely 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/cnga1-p-gln415pro (accessed [today's date]).

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