Is CROCC p.Ser188= (c.564G>A) pathogenic?

CROCC p.Ser188= (c.564G>A) is classified Likely benign in CROCC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Rare (popmax 0.128%, nfe).

How common is CROCC p.Ser188= (c.564G>A) in the general population?

CROCC p.Ser188= (c.564G>A) is rare (popmax 0.128%, nfe) (gnomAD).

CROCC p.Ser188=

c.564G>A · rs149095491 · VCV2638366

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.128%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.7	GERP -3.1
Overall
CADD	0.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.128% European (non-Finnish) · 1,496/1,170,770 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.106% 1,690/1,594,240 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.168%	594
European (non-Finnish)grpmax	0.128%	783
Admixed American	0.0473%	2,112
Remaining individualsnot grpmax-eligible	0.0405%	2,469
African / African-American	0.0281%	3,554
East Asian	0.0204%	4,902
Middle Eastern	0.0181%	5,538
South Asian	0.00683%	14,651

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser188=
Coding: c.564G>A
MANE Select: NM_014675
dbSNP: rs149095491
Type: single nucleotide variant
Location: chr1:16930150 (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.Ser188Leu 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-ser188 (accessed [today's date]).

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