Is GUCY2C p.Arg792Lys (c.2375G>A) pathogenic?

GUCY2C p.Arg792Lys (c.2375G>A) is classified Uncertain significance in GUCY2C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely pathogenic (0.7312); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GUCY2C p.Arg792Lys (c.2375G>A)?

GUCY2C p.Arg792Lys (c.2375G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GUCY2C p.Arg792Lys (c.2375G>A) in the general population?

GUCY2C p.Arg792Lys (c.2375G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GUCY2C p.Arg792Lys (c.2375G>A)?

AlphaMissense predicts likely pathogenic (score 0.7312) — an in-silico prediction, not a clinical call.

GUCY2C p.Arg792Lys

c.2375G>A · rs2497633636 · VCV2274493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7312 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7312	likely pathogenic
REVEL	0.353	indeterminate
SaProt	LLR -1.03	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 83 kb · p 7.2e-05 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GUCY2C
Protein: p.Arg792Lys
Coding: c.2375G>A
MANE Select: NM_004963
dbSNP: rs2497633636
Type: single nucleotide variant
Location: chr12:14625790 (GRCh38)
Gene constraint: LOEUF 1.118 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.08 · 3 PDB

Full GUCY2C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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GUCY2C p.Arg114Trp Uncertain significance ★★ ⚠ same condition
GUCY2C p.Arg319Gln Uncertain significance ★★ ⚠ same condition
GUCY2C p.Arg570Gln Uncertain significance ★★ ⚠ same condition
GUCY2C p.Arg686Gln Uncertain significance ★★ ⚠ same condition
GUCY2C p.Arg686Trp 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/gucy2c-p-arg792lys (accessed [today's date]).

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