Is LRRC56 p.Ser35= (c.105C>T) pathogenic?

LRRC56 p.Ser35= (c.105C>T) is classified Likely benign in LRRC56 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). Absent from gnomAD v4.1.

How common is LRRC56 p.Ser35= (c.105C>T) in the general population?

LRRC56 p.Ser35= (c.105C>T) is absent from gnomAD v4.1 (gnomAD).

LRRC56 p.Ser35=

c.105C>T · rs2539848153 · VCV2844669

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 3.2	GERP 0.12, phastCons 1
Overall
CADD	12.84	PHRED · no single calibrated threshold — expert panels disagree

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: LRRC56
Protein: p.Ser35=
Coding: c.105C>T
MANE Select: NM_198075
dbSNP: rs2539848153
Type: single nucleotide variant
Location: chr11:540789 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.07

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

Similar variants

HRAS p.Thr35Ala Uncertain significance ★ ⚠ same residue
LRRC56 p.Ser35Asn Uncertain significance ★ ⚠ 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

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-ser35 (accessed [today's date]).

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