Is CNGA4 p.Pro17Ser (c.49C>T) pathogenic?

CNGA4 p.Pro17Ser (c.49C>T) is classified Uncertain significance in CNGA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0673); Ultra-rare (popmax 0.0217%, amr).

How common is CNGA4 p.Pro17Ser (c.49C>T) in the general population?

CNGA4 p.Pro17Ser (c.49C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about CNGA4 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

CNGA4 p.Pro17Ser

c.49C>T · rs767349046 · VCV3146454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -6.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.39	GERP -1.4
Regional constraint	o/e 0.96	unconstrained · MANE · 5,199 bp · p 0.29 · regional, not allelic
Overall
CADD	0.571	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/60,004 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.000867% 14/1,614,052 alleles · ultra-rare exomes 11/1,461,846 · genomes 3/152,206 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,616
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: CNGA4
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_001037329
dbSNP: rs767349046
Type: single nucleotide variant
Location: chr11:6239255 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.01 · 2 PDB

Full CNGA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNGA4 c.917+10C>T Benign ★★ same type
CNGA4 p.Glu553Val Benign ★★ same type
CNGA4 p.Thr157Ala Benign ★★ same type
CNGA4 p.Ala120Pro Uncertain significance ★ ⚠ same type
CNGA4 p.Ala207Thr Uncertain significance ★ ⚠ same type
CNGA4 p.Ala254Asp Uncertain significance ★ ⚠ same type
CNGA4 p.Ala488Thr Uncertain significance ★ ⚠ same type
CNGA4 p.Ala516Gly Uncertain significance ★ ⚠ 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/cnga4-p-pro17ser (accessed [today's date]).

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