Is CROCC p.Arg1908Cys (c.5722C>T) pathogenic?

CROCC p.Arg1908Cys (c.5722C>T) is classified Benign in CROCC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-01). AlphaMissense: likely benign (0.2217); Low-frequency (popmax 1.1%, mid).

How common is CROCC p.Arg1908Cys (c.5722C>T) in the general population?

CROCC p.Arg1908Cys (c.5722C>T) is low-frequency (popmax 1.1%, mid) (gnomAD).

What do computational predictors say about CROCC p.Arg1908Cys (c.5722C>T)?

AlphaMissense predicts likely benign (score 0.2217) — an in-silico prediction, not a clinical call.

CROCC p.Arg1908Cys

c.5722C>T · rs147926226 · VCV771109

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2217 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.1%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2217	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 18 kb · p 0.057 · regional, not allelic
Overall
CADD	29.9	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

Grpmax group 1.1% Middle Eastern · 60/5,460 alleles

Filtering AF 0.876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.796%

Overall 0.27% 4,336/1,604,400 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.1%	91
Ashkenazi Jewishnot grpmax-eligible	0.785%	127
South Asian	0.357%	280
European (non-Finnish)	0.288%	347
Remaining individualsnot grpmax-eligible	0.276%	362
Admixed American	0.165%	605
Finnishnot grpmax-eligible	0.0566%	1,767
African / African-American	0.0495%	2,018
East Asian	0.00447%	22,373

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.Arg1908Cys
Coding: c.5722C>T
MANE Select: NM_014675
dbSNP: rs147926226
Type: single nucleotide variant
Location: chr1:16970705 (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.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.Arg675His Benign ★★ same type
CROCC p.Arg691His Benign ★★ same type
CROCC p.Arg903Ser Benign/Likely benign ★★ same type
CROCC p.Gln302Glu Benign/Likely 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-arg1908cys (accessed [today's date]).

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