Is CNGA1 p.Asp210Val (c.629A>T) pathogenic?

CNGA1 p.Asp210Val (c.629A>T) is classified Uncertain significance in CNGA1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9942); Very rare (popmax 0.000512%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with CNGA1 p.Asp210Val (c.629A>T)?

CNGA1 p.Asp210Val (c.629A>T) is associated with inherited retinal dystrophy (ClinVar).

How common is CNGA1 p.Asp210Val (c.629A>T) in the general population?

CNGA1 p.Asp210Val (c.629A>T) is very rare (popmax 0.000512%, nfe) (gnomAD).

What do computational predictors say about CNGA1 p.Asp210Val (c.629A>T)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

CNGA1 p.Asp210Val

c.629A>T · rs775886085 · VCV236442

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000512%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic · top 8% in CNGA1
REVEL	0.872	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 4.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 D214V vs ClinVar D210V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000512% European (non-Finnish) · 6/1,172,804 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000413% 6/1,453,512 alleles · very rare

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.Asp210Val
Coding: c.629A>T
MANE Select: NM_001379270
dbSNP: rs775886085
Type: single nucleotide variant
Location: chr4:47940786 (GRCh38)
Gene constraint: LOEUF 0.779 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.88 · 19 PDB
Residue 210: 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-asp210val (accessed [today's date]).

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