Is CNGA2 p.Glu645Asp (c.1935A>C) pathogenic?

CNGA2 p.Glu645Asp (c.1935A>C) is classified Uncertain significance in CNGA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.0475%, eas).

How common is CNGA2 p.Glu645Asp (c.1935A>C) in the general population?

CNGA2 p.Glu645Asp (c.1935A>C) is ultra-rare (popmax 0.0475%, eas) (gnomAD).

What do computational predictors say about CNGA2 p.Glu645Asp (c.1935A>C)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

CNGA2 p.Glu645Asp

c.1935A>C · rs748014247 · VCV3146443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0475%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -6.96	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 0.097	phastCons 0.55
Regional constraint	o/e 1.05	unconstrained · MANE · 6,011 bp · p 0.29 · regional, not allelic
Overall
CADD	4.02	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 0.0475% East Asian · 16/33,673 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0243%

Overall 0.00133% 16/1,204,888 alleles · ultra-rare exomes 13/1,093,349 · genomes 3/111,539 · joint denominator

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: CNGA2
Protein: p.Glu645Asp
Coding: c.1935A>C
MANE Select: NM_005140
dbSNP: rs748014247
Type: single nucleotide variant
Location: chrX:151744438 (GRCh38)
Structure: AlphaFold pLDDT 78.41 · 2 PDB
Residue 645: the 'disordered' region

Full CNGA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNGA2 p.Arg399Gln Benign ★★ same type
CNGA2 p.Asn15Thr Benign ★★ same type
CNGA2 p.Gln509= Benign ★★ same type
CNGA2 p.Gly113Val Benign ★★ same type
CNGA2 p.Leu619= Benign ★★ same type
CNGA2 p.Ala290Val Uncertain significance ★ ⚠ same type
CNGA2 p.Ala383Thr Uncertain significance ★ ⚠ same type
CNGA2 p.Ala407Thr 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/cnga2-p-glu645asp (accessed [today's date]).

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