Is CROCC p.Arg809Ter (c.2425C>T) pathogenic?

CROCC p.Arg809Ter (c.2425C>T) is classified Uncertain significance in CROCC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). Rare (popmax 0.382%, afr).

How common is CROCC p.Arg809Ter (c.2425C>T) in the general population?

CROCC p.Arg809Ter (c.2425C>T) is rare (popmax 0.382%, afr) (gnomAD).

CROCC p.Arg809Ter

c.2425C>T · VCV4958546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.382%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 37
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.19, phastCons 0.93
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.382% African / African-American · 282/73,882 alleles

Filtering AF 0.345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.331%

Overall 0.0224% 351/1,563,754 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.382%	262
Admixed American	0.0344%	2,904
Remaining individualsnot grpmax-eligible	0.0297%	3,368
East Asian	0.00713%	14,029
South Asian	0.00354%	28,287
European (non-Finnish)	0.00234%	42,764

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: CROCC
Protein: p.Arg809Ter
Coding: c.2425C>T
MANE Select: NM_014675
Type: single nucleotide variant
Location: chr1:16946902 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.58 · 2 PDB

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

Similar variants

CROCC p.Arg809Gln Uncertain significance ★ ⚠ same residue
CROCC p.Arg1094Trp Uncertain significance ★★ ⚠ same type
CROCC p.Asp1119His Uncertain significance ★★ ⚠ same type
CROCC p.Gly486Arg Uncertain significance ★★ ⚠ same type
CROCC p.Arg1729Gln Likely benign ★★ same type
CROCC p.Arg1908Cys Benign ★★ ⚠ same type
CROCC p.Arg675His Benign ★★ same type
CROCC p.Arg691His Benign ★★ 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/crocc-p-arg809ter (accessed [today's date]).

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