Is LRBA p.Pro1716Arg (c.5147C>G) pathogenic?

LRBA p.Pro1716Arg (c.5147C>G) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely benign (0.1206); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Pro1716Arg (c.5147C>G)?

LRBA p.Pro1716Arg (c.5147C>G) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Pro1716Arg (c.5147C>G) in the general population?

LRBA p.Pro1716Arg (c.5147C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about LRBA p.Pro1716Arg (c.5147C>G)?

AlphaMissense predicts likely benign (score 0.1206) — an in-silico prediction, not a clinical call.

LRBA p.Pro1716Arg

c.5147C>G · VCV4099367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1206	likely benign
REVEL	0.294	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,022 alleles

Overall 6.84e-05% 1/1,461,782 alleles · very rare

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: LRBA
Protein: p.Pro1716Arg
Coding: c.5147C>G
MANE Select: NM_001364905
Type: single nucleotide variant
Location: chr4:150828204 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI <0.01 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRBA p.Pro1716= Likely benign ★★ same residue
LRBA p.Ala2007Val Uncertain significance ★★ same condition
LRBA p.Ala394Pro Uncertain significance ★★ same condition
LRBA p.Ala627Thr Uncertain significance ★★ ⚠ same condition
LRBA p.Arg1305Pro Uncertain significance ★★ ⚠ same condition
LRBA p.Arg1505Gly Uncertain significance ★★ ⚠ same condition
LRBA p.Arg167Ser Uncertain significance ★★ ⚠ same condition
LRBA p.Arg2128Leu Uncertain significance ★★ ⚠ same condition

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/lrba-p-pro1716arg (accessed [today's date]).

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