Is CNGA1 p.Ser238Pro (c.712T>C) pathogenic?

CNGA1 p.Ser238Pro (c.712T>C) is classified Uncertain significance in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-28). AlphaMissense: likely pathogenic (0.7461); Absent from gnomAD v4.1.

How common is CNGA1 p.Ser238Pro (c.712T>C) in the general population?

CNGA1 p.Ser238Pro (c.712T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNGA1 p.Ser238Pro (c.712T>C)?

AlphaMissense predicts likely pathogenic (score 0.7461) — an in-silico prediction, not a clinical call.

CNGA1 p.Ser238Pro

c.712T>C · rs2475753746 · VCV2118787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7461 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.7461	likely pathogenic
REVEL	0.471	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	18.64	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S242P vs ClinVar S238P) — 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.Ser238Pro
Coding: c.712T>C
MANE Select: NM_001379270
dbSNP: rs2475753746
Type: single nucleotide variant
Location: chr4:47937770 (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

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-ser238pro (accessed [today's date]).

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