Is CNGA1 p.Phe12Ser (c.35T>C) pathogenic?

CNGA1 p.Phe12Ser (c.35T>C) is classified Uncertain significance in CNGA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-15). AlphaMissense: likely benign (0.0897); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CNGA1 p.Phe12Ser (c.35T>C)?

CNGA1 p.Phe12Ser (c.35T>C) is associated with Inborn genetic diseases, retinitis pigmentosa (ClinVar).

How common is CNGA1 p.Phe12Ser (c.35T>C) in the general population?

CNGA1 p.Phe12Ser (c.35T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNGA1 p.Phe12Ser (c.35T>C)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

CNGA1 p.Phe12Ser

c.35T>C · rs981071919 · VCV900311

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.179	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 4.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	17.28	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F16S vs ClinVar F12S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNGA1
Protein: p.Phe12Ser
Coding: c.35T>C
MANE Select: NM_001379270
dbSNP: rs981071919
Type: single nucleotide variant
Location: chr4:47952655 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB

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

Also linked: retinitis pigmentosa

Similar variants

CNGA1 p.Phe12= Likely benign ★★ same residue
CNGA1 c.546-1G>C Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Arg214Ter Pathogenic ★★ same condition
CNGA1 p.Arg28Ter Pathogenic ★★ same condition
CNGA1 p.Arg510Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Ser316Phe Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Ser348Arg Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Tyr78Ter Pathogenic/Likely pathogenic ★★ 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-phe12ser (accessed [today's date]).

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