Is LBHD1 p.Val43Phe (c.127G>T) pathogenic?

LBHD1 p.Val43Phe (c.127G>T) is classified Uncertain significance in LBHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1839); Very rare (popmax 0.00799%, afr).

How common is LBHD1 p.Val43Phe (c.127G>T) in the general population?

LBHD1 p.Val43Phe (c.127G>T) is very rare (popmax 0.00799%, afr) (gnomAD).

What do computational predictors say about LBHD1 p.Val43Phe (c.127G>T)?

AlphaMissense predicts likely benign (score 0.1839) — an in-silico prediction, not a clinical call.

LBHD1 p.Val43Phe

c.127G>T · VCV4545914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00799%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1839	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.83	GERP -4.9
Regional constraint	o/e 1.08	unconstrained · MANE · 6,899 bp · p 0.13 · regional, not allelic
Overall
CADD	0.815	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 0.00799% African / African-American · 6/75,048 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000434% 7/1,614,210 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00799%	12,508
Admixed American	0.00167%	60,016

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.Val43Phe
Coding: c.127G>T
MANE Select: NM_024099
Type: single nucleotide variant
Location: chr11:62669905 (GRCh38)
Gene constraint: LOEUF 1.281 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.51
Residue 43: the lbh domain

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

Similar variants

UQCC3 p.Pro43Leu Uncertain significance ★ same residue
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

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-val43phe (accessed [today's date]).

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