Is BLVRB p.Pro122Ser (c.364C>T) pathogenic?

BLVRB p.Pro122Ser (c.364C>T) is classified Uncertain significance in BLVRB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-20). AlphaMissense: likely pathogenic (0.6317); Ultra-rare (popmax 0.0373%, nfe).

How common is BLVRB p.Pro122Ser (c.364C>T) in the general population?

BLVRB p.Pro122Ser (c.364C>T) is ultra-rare (popmax 0.0373%, nfe) (gnomAD).

What do computational predictors say about BLVRB p.Pro122Ser (c.364C>T)?

AlphaMissense predicts likely pathogenic (score 0.6317) — an in-silico prediction, not a clinical call.

BLVRB p.Pro122Ser

c.364C>T · rs139843463 · VCV2268463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6317 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6317	likely pathogenic
REVEL	0.472	indeterminate
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.6 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% European (non-Finnish) · 440/1,179,708 alleles

Filtering AF 0.0344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0333%

Overall 0.0283% 456/1,613,320 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0373%	2,681
Remaining individualsnot grpmax-eligible	0.0128%	7,809
African / African-American	0.00533%	18,753
Finnishnot grpmax-eligible	0.00469%	21,323
South Asian	0.0011%	90,882

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: BLVRB
Protein: p.Pro122Ser
Coding: c.364C>T
MANE Select: NM_000713
dbSNP: rs139843463
Type: single nucleotide variant
Location: chr19:40451463 (GRCh38)
Gene constraint: LOEUF 1.718 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.71 · 23 PDB

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

Similar variants

BLVRB p.Arg140Gly Likely benign ★★ same type
BLVRB p.Arg46Gln Likely benign ★★ same type
BLVRB p.Thr84= Benign ★★ same type
BLVRB p.Ala162Val Uncertain significance ★ ⚠ same type
BLVRB p.Ala21Thr Uncertain significance ★ ⚠ same type
BLVRB p.Ala26Thr Uncertain significance ★ ⚠ same type
BLVRB p.Ala7Val Uncertain significance ★ ⚠ same type
BLVRB p.Ala91Thr Uncertain significance ★ ⚠ 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/blvrb-p-pro122ser (accessed [today's date]).

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