Is CNGA1 p.Val430Phe (c.1288G>T) pathogenic?

CNGA1 p.Val430Phe (c.1288G>T) is classified Uncertain significance in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely pathogenic (0.9852); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CNGA1 p.Val430Phe (c.1288G>T)?

CNGA1 p.Val430Phe (c.1288G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CNGA1 p.Val430Phe (c.1288G>T) in the general population?

CNGA1 p.Val430Phe (c.1288G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CNGA1 p.Val430Phe (c.1288G>T)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

CNGA1 p.Val430Phe

c.1288G>T · VCV4615977

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic
REVEL	0.951	strongly 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 7.7	GERP 4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	26.1	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 V434F vs ClinVar V430F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,860 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.Val430Phe
Coding: c.1288G>T
MANE Select: NM_001379270
Type: single nucleotide variant
Location: chr4:47937194 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 430: the 'c-linker' region; an α-helix

Full CNGA1 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

CNGA1 p.Val430Ile Uncertain significance ★★ same residue
CNGA1 p.Ala408Val Uncertain significance ★★ ⚠ same condition
CNGA1 p.Ala524Ser Uncertain significance ★★ same condition
CNGA1 p.Arg510Gln Uncertain significance ★★ ⚠ same condition
CNGA1 p.Arg625Gln Uncertain significance ★★ ⚠ same condition
CNGA1 p.Arg639Gln Uncertain significance ★★ same condition
CNGA1 p.Asp245Tyr Uncertain significance ★★ ⚠ same condition
CNGA1 p.Asp536Asn 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/cnga1-p-val430phe (accessed [today's date]).

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