Is CNGA1 p.Asp684Val (c.2051A>T) pathogenic?

CNGA1 p.Asp684Val (c.2051A>T) is classified Uncertain significance in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-19). AlphaMissense: likely benign (0.1066); Absent from gnomAD v4.1.

How common is CNGA1 p.Asp684Val (c.2051A>T) in the general population?

CNGA1 p.Asp684Val (c.2051A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNGA1 p.Asp684Val (c.2051A>T)?

AlphaMissense predicts likely benign (score 0.1066) — an in-silico prediction, not a clinical call.

CNGA1 p.Asp684Val

c.2051A>T · rs2475744601 · VCV2114474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1066 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.1066	likely benign
REVEL	0.476	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 3.5, phastCons 0.97
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	19.67	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 D688V vs ClinVar D684V) — 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.Asp684Val
Coding: c.2051A>T
MANE Select: NM_001379270
dbSNP: rs2475744601
Type: single nucleotide variant
Location: chr4:47936431 (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 p.Asp684Asn Uncertain significance ★ ⚠ same residue
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

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-asp684val (accessed [today's date]).

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