Is CRX p.Pro127His (c.380C>A) pathogenic?

CRX p.Pro127His (c.380C>A) is classified Uncertain significance in CRX (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-01). AlphaMissense: likely benign (0.1154); Absent from gnomAD v4.1.

How common is CRX p.Pro127His (c.380C>A) in the general population?

CRX p.Pro127His (c.380C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRX p.Pro127His (c.380C>A)?

AlphaMissense predicts likely benign (score 0.1154) — an in-silico prediction, not a clinical call.

CRX p.Pro127His

c.380C>A · rs1968163788 · VCV872653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1154 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1154	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -8.75	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 3.4	GERP 0.5, phastCons 0.16
Regional constraint	o/e 0.94	unconstrained · MANE · 622 bp · p 0.35 · regional, not allelic
Overall
CADD	19.79	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: CRX
Protein: p.Pro127His
Coding: c.380C>A
MANE Select: NM_000554
dbSNP: rs1968163788
Type: single nucleotide variant
Location: chr19:47839447 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI 0.72 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 61.78 · 1 PDB
Residue 127: the 'disordered' region

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

Similar variants

CRX p.Pro127Leu Uncertain significance ★★ ⚠ same residue
CRX c.101-1G>A Pathogenic/Likely pathogenic ★★ same type
CRX p.Arg40Gln Pathogenic/Likely pathogenic ★★ same type
CRX p.Arg40Trp Pathogenic/Likely pathogenic ★★ same type
CRX p.Arg41Gln Pathogenic/Likely pathogenic ★★ same type
CRX p.Arg41Pro Likely pathogenic ★★ same type
CRX p.Arg43Cys Pathogenic ★★ same type
CRX p.Arg43His 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/crx-p-pro127his (accessed [today's date]).

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