Is LRBA p.Pro210Leu (c.629C>T) pathogenic?

LRBA p.Pro210Leu (c.629C>T) is classified Uncertain significance in LRBA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-19). AlphaMissense: ambiguous (0.3704); Very rare (popmax 0.0033%, sas); Associated with Inborn genetic diseases.

What condition is associated with LRBA p.Pro210Leu (c.629C>T)?

LRBA p.Pro210Leu (c.629C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRBA p.Pro210Leu (c.629C>T) in the general population?

LRBA p.Pro210Leu (c.629C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about LRBA p.Pro210Leu (c.629C>T)?

AlphaMissense predicts ambiguous (score 0.3704) — an in-silico prediction, not a clinical call.

LRBA p.Pro210Leu

c.629C>T · rs1258011984 · VCV2302150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3704 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3704	ambiguous
REVEL	0.518	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.43	donor loss, 16 bp away · masked 0 · deltas
Pangolin	Δ0.32	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 10	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 749 kb · p 0.0015 · regional, not allelic
Overall
CADD	24.8	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 0.0033% South Asian · 3/90,914 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,609,636 alleles · very rare exomes 3/1,457,442 · genomes 0/152,194 · joint denominator

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.Pro210Leu
Coding: c.629C>T
MANE Select: NM_001364905
dbSNP: rs1258011984
Type: single nucleotide variant
Location: chr4:150921214 (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.Pro210= 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-pro210leu (accessed [today's date]).

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