Is LBHD1 p.Ser251Arg (c.753C>G) pathogenic?

LBHD1 p.Ser251Arg (c.753C>G) is classified Uncertain significance in LBHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1331); Absent from gnomAD v4.1.

How common is LBHD1 p.Ser251Arg (c.753C>G) in the general population?

LBHD1 p.Ser251Arg (c.753C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LBHD1 p.Ser251Arg (c.753C>G)?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

LBHD1 p.Ser251Arg

c.753C>G · rs2539068099 · VCV2557949

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 8.5	GERP 0.89, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 6,899 bp · p 0.13 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A85G vs ClinVar S251R) — verify the residue.

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: LBHD1
Protein: p.Ser251Arg
Coding: c.753C>G
MANE Select: NM_001286086 · reported on NM_024099
dbSNP: rs2539068099
Type: single nucleotide variant
Location: chr11:62663244 (GRCh38)

Full LBHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/lbhd1-p-ser251arg (accessed [today's date]).

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