Is LRRC56 p.Pro233= (c.699G>A) pathogenic?

LRRC56 p.Pro233= (c.699G>A) is classified Benign/Likely benign in LRRC56 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-07). Rare (popmax 0.382%, eas).

How common is LRRC56 p.Pro233= (c.699G>A) in the general population?

LRRC56 p.Pro233= (c.699G>A) is rare (popmax 0.382%, eas) (gnomAD).

LRRC56 p.Pro233=

c.699G>A · rs557846022 · VCV1656882

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.382%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -2.7
Overall
CADD	0.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.382% East Asian · 155/40,598 alleles

Filtering AF 0.333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.314%

Overall 0.0482% 745/1,546,068 alleles · rare exomes 628/1,394,164 · genomes 117/151,904 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.463%	216
East Asiangrpmax	0.382%	262
Remaining individualsnot grpmax-eligible	0.0635%	1,575
European (non-Finnish)	0.0231%	4,335
Middle Eastern	0.0167%	5,972
Admixed American	0.0138%	7,257
South Asian	0.0119%	8,370

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: LRRC56
Protein: p.Pro233=
Coding: c.699G>A
MANE Select: NM_198075
dbSNP: rs557846022
Type: single nucleotide variant
Location: chr11:551205 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.07
Residue 233: the lrrct domain

Full LRRC56 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRRC56 p.Pro233Leu Benign ★★ same residue
HRAS c.291-6T>G Benign ★★★ same type
HRAS p.Gly12= Likely benign ★★★ same type
LRRC56 p.Tyr53Ter Pathogenic/Likely pathogenic ★★ same type
HRAS p.Arg68Gly Uncertain significance ★★ ⚠ same type
HRAS p.Lys88Arg Uncertain significance ★★ ⚠ same type
HRAS p.Met111Leu Uncertain significance ★★ same type
HRAS p.Pro174Ala 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/lrrc56-p-pro233 (accessed [today's date]).

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