Is CNGA1 p.Val623Phe (c.1867G>T) pathogenic?

CNGA1 p.Val623Phe (c.1867G>T) is classified Uncertain significance in CNGA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-18). AlphaMissense: ambiguous (0.5485); Ultra-rare (popmax 0.0329%, mid); Associated with inherited retinal dystrophy.

What condition is associated with CNGA1 p.Val623Phe (c.1867G>T)?

CNGA1 p.Val623Phe (c.1867G>T) is associated with inherited retinal dystrophy (ClinVar).

How common is CNGA1 p.Val623Phe (c.1867G>T) in the general population?

CNGA1 p.Val623Phe (c.1867G>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CNGA1 p.Val623Phe (c.1867G>T)?

AlphaMissense predicts ambiguous (score 0.5485) — an in-silico prediction, not a clinical call.

CNGA1 p.Val623Phe

c.1867G>T · rs758429898 · VCV837882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5485 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.5485	ambiguous
REVEL	0.714	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	25.1	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 V627F vs ClinVar V623F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000682% 11/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
African / African-American	0.00134%	74,906
European (non-Finnish)	0.000678%	147,502

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.Val623Phe
Coding: c.1867G>T
MANE Select: NM_001379270
dbSNP: rs758429898
Type: single nucleotide variant
Location: chr4:47936615 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 623: an α-helix

Full CNGA1 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

CNGA1 p.Arg214Ter Pathogenic ★★ same condition
CNGA1 p.Arg28Ter Pathogenic ★★ same condition
CNGA1 p.Arg420Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Arg510Ter Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Ser316Phe Pathogenic/Likely pathogenic ★★ same condition
CNGA1 p.Asp500Gly Uncertain significance ★★ same condition
CNGA1 p.Gly218Asp Uncertain significance ★★ ⚠ same condition
CNGA1 p.Thr656Ile 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-val623phe (accessed [today's date]).

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