Is CNGA1 p.Ser614Arg (c.1842T>A) pathogenic?

CNGA1 p.Ser614Arg (c.1842T>A) is classified Uncertain significance in CNGA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: ambiguous (0.3605); Very rare (popmax 0.00934%, afr).

How common is CNGA1 p.Ser614Arg (c.1842T>A) in the general population?

CNGA1 p.Ser614Arg (c.1842T>A) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about CNGA1 p.Ser614Arg (c.1842T>A)?

AlphaMissense predicts ambiguous (score 0.3605) — an in-silico prediction, not a clinical call.

CNGA1 p.Ser614Arg

c.1842T>A · rs769653731 · VCV1928530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3605 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Computational evidence

Protein change
AlphaMissense	0.3605	ambiguous
REVEL	0.436	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -5.3, phastCons 0.059
Regional constraint	o/e 0.91	unconstrained · MANE · 16 kb · p 0.011 · regional, not allelic
Overall
CADD	10.73	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 S618R vs ClinVar S614R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,930 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,614,068 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,704
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ser614Arg
Coding: c.1842T>A
MANE Select: NM_001379270
dbSNP: rs769653731
Type: single nucleotide variant
Location: chr4:47936640 (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-ser614arg (accessed [today's date]).

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