Is CRHR2 p.Pro394Ser (c.1180C>T) pathogenic?

CRHR2 p.Pro394Ser (c.1180C>T) is classified Uncertain significance in CRHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-14). AlphaMissense: likely benign (0.2319); Absent from gnomAD v4.1.

How common is CRHR2 p.Pro394Ser (c.1180C>T) in the general population?

CRHR2 p.Pro394Ser (c.1180C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRHR2 p.Pro394Ser (c.1180C>T)?

AlphaMissense predicts likely benign (score 0.2319) — an in-silico prediction, not a clinical call.

CRHR2 p.Pro394Ser

c.1180C>T · rs2534364041 · VCV2301722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2319 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2319	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -6.23	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 29 kb · p 0.65 · regional, not allelic
Overall
CADD	27.4	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

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: CRHR2
Protein: p.Pro394Ser
Coding: c.1180C>T
MANE Select: NM_001883
dbSNP: rs2534364041
Type: single nucleotide variant
Location: chr7:30653516 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.80 · 6 PDB

Full CRHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRHR2 p.Arg114Cys Uncertain significance ★ ⚠ same type
CRHR2 p.Arg142Trp Uncertain significance ★ ⚠ same type
CRHR2 p.Arg145Cys Uncertain significance ★ ⚠ same type
CRHR2 p.Arg145Leu Uncertain significance ★ ⚠ same type
CRHR2 p.Arg148Trp Uncertain significance ★ ⚠ same type
CRHR2 p.Arg221Cys Uncertain significance ★ ⚠ same type
CRHR2 p.Arg221His Uncertain significance ★ ⚠ same type
CRHR2 p.Arg223His 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/crhr2-p-pro394ser (accessed [today's date]).

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