Is LBHD1 p.Ser8Arg (c.24C>G) pathogenic?

LBHD1 p.Ser8Arg (c.24C>G) is classified Uncertain significance in LBHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: ambiguous (0.5241); Ultra-rare (popmax 0.0229%, nfe).

How common is LBHD1 p.Ser8Arg (c.24C>G) in the general population?

LBHD1 p.Ser8Arg (c.24C>G) is ultra-rare (popmax 0.0229%, nfe) (gnomAD).

What do computational predictors say about LBHD1 p.Ser8Arg (c.24C>G)?

AlphaMissense predicts ambiguous (score 0.5241) — an in-silico prediction, not a clinical call.

LBHD1 p.Ser8Arg

c.24C>G · VCV3290207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5241 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0229%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5241	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -6.02	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.76	GERP -3
Regional constraint	o/e 1.08	unconstrained · MANE · 6,899 bp · p 0.13 · regional, not allelic
Overall
CADD	6.492	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 0.0229% European (non-Finnish) · 270/1,179,454 alleles

Filtering AF 0.0206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.0176% 284/1,612,746 alleles · ultra-rare exomes 261/1,460,534 · genomes 23/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0229%	4,368
Remaining individualsnot grpmax-eligible	0.00961%	10,402
Admixed American	0.00834%	11,990
African / African-American	0.004%	24,973

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: LBHD1
Protein: p.Ser8Arg
Coding: c.24C>G
MANE Select: NM_024099
Type: single nucleotide variant
Location: chr11:62670008 (GRCh38)
Gene constraint: LOEUF 1.281 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.51
Residue 8: the lbh domain; the 'disordered' region

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

Similar variants

UQCC3 p.Arg48Lys Uncertain significance ★★ ⚠ same type
UQCC3 p.Glu52Ala Uncertain significance ★★ ⚠ same type
UQCC3 c.121-11C>T Benign ★★ same type
UQCC3 c.-399G>T Benign ★★ same type
UQCC3 p.Gly86Ser Likely benign ★★ same type
UQCC3 p.Gly89Ser Benign ★★ same type
UQCC3 p.Thr69Ile Likely benign ★★ same type
UQCC3 p.Trp76Gly 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/lbhd1-p-ser8arg (accessed [today's date]).

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