Is LBHD1 p.Pro31Ser (c.91C>T) pathogenic?

LBHD1 p.Pro31Ser (c.91C>T) is classified Uncertain significance in LBHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.1334); Ultra-rare (popmax 0.02%, afr).

How common is LBHD1 p.Pro31Ser (c.91C>T) in the general population?

LBHD1 p.Pro31Ser (c.91C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about LBHD1 p.Pro31Ser (c.91C>T)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

LBHD1 p.Pro31Ser

c.91C>T · VCV4096797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2, phastCons 0.006
Regional constraint	o/e 1.08	unconstrained · MANE · 6,899 bp · p 0.13 · regional, not allelic
Overall
CADD	16.04	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% African / African-American · 15/74,918 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00105% 17/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,995
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Pro31Ser
Coding: c.91C>T
MANE Select: NM_024099
Type: single nucleotide variant
Location: chr11:62669941 (GRCh38)
Gene constraint: LOEUF 1.281 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.51
Residue 31: 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-pro31ser (accessed [today's date]).

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