Is CNGA3 p.Pro271Ser (c.811C>T) pathogenic?

CNGA3 p.Pro271Ser (c.811C>T) is classified Likely pathogenic in CNGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-01). AlphaMissense: likely pathogenic (0.5673); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with CNGA3 p.Pro271Ser (c.811C>T)?

CNGA3 p.Pro271Ser (c.811C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is CNGA3 p.Pro271Ser (c.811C>T) in the general population?

CNGA3 p.Pro271Ser (c.811C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNGA3 p.Pro271Ser (c.811C>T)?

AlphaMissense predicts likely pathogenic (score 0.5673) — an in-silico prediction, not a clinical call.

CNGA3 p.Pro271Ser

c.811C>T · VCV3249037

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5673 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.5673	likely pathogenic ✓ concordant with ClinVar
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,336 bp · p 0.34 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

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

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: CNGA3
Protein: p.Pro271Ser
Coding: c.811C>T
MANE Select: NM_001298
Type: single nucleotide variant
Location: chr2:98395981 (GRCh38)
Gene constraint: LOEUF 1.126 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.33 · 10 PDB
Residue 271: an α-helix

Full CNGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CNGA3 p.Pro271Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CNGA3 p.Pro271Thr Likely pathogenic ⚠ same residue
CNGA3 p.Ala262Pro Likely pathogenic ★★ ⚠ same condition
CNGA3 p.Arg277Cys Pathogenic/Likely pathogenic ★★ same condition
CNGA3 p.Arg277His Pathogenic ★★ same condition
CNGA3 p.Arg283Gln Pathogenic ★★ ⚠ same condition
CNGA3 p.Arg283Trp Pathogenic/Likely pathogenic ★★ same condition
CNGA3 p.Arg427Cys 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/cnga3-p-pro271ser (accessed [today's date]).

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