Is LBHD1 p.Pro104Arg (c.311C>G) pathogenic?

LBHD1 p.Pro104Arg (c.311C>G) is classified Uncertain significance in LBHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.251); Ultra-rare (popmax 0.0987%, afr).

How common is LBHD1 p.Pro104Arg (c.311C>G) in the general population?

LBHD1 p.Pro104Arg (c.311C>G) is ultra-rare (popmax 0.0987%, afr) (gnomAD).

What do computational predictors say about LBHD1 p.Pro104Arg (c.311C>G)?

AlphaMissense predicts likely benign (score 0.251) — an in-silico prediction, not a clinical call.

LBHD1 p.Pro104Arg

c.311C>G · rs142209878 · VCV2527767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.251 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.251	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 6,899 bp · p 0.13 · regional, not allelic
Overall
CADD	23.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P130R vs ClinVar P104R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0987% African / African-American · 74/74,964 alleles

Filtering AF 0.0806% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0739%

Overall 0.00509% 82/1,612,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0987%	1,013
Remaining individualsnot grpmax-eligible	0.00641%	15,601
Admixed American	0.00167%	59,896
South Asian	0.0011%	90,864
European (non-Finnish)	0.00017%	589,494

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.Pro104Arg
Coding: c.311C>G
MANE Select: NM_024099
dbSNP: rs142209878
Type: single nucleotide variant
Location: chr11:62669643 (GRCh38)
Gene constraint: LOEUF 1.281 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.51
Residue 104: the lbh domain

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-pro104arg (accessed [today's date]).

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