Is B9D1 p.Pro142Ser (c.424C>T) pathogenic?

B9D1 p.Pro142Ser (c.424C>T) is classified Uncertain significance in B9D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely pathogenic (0.9673); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with B9D1 p.Pro142Ser (c.424C>T)?

B9D1 p.Pro142Ser (c.424C>T) is associated with Inborn genetic diseases (ClinVar).

How common is B9D1 p.Pro142Ser (c.424C>T) in the general population?

B9D1 p.Pro142Ser (c.424C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about B9D1 p.Pro142Ser (c.424C>T)?

AlphaMissense predicts likely pathogenic (score 0.9673) — an in-silico prediction, not a clinical call.

B9D1 p.Pro142Ser

c.424C>T · VCV4594306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9673 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9673	likely pathogenic
REVEL	0.75	pathogenic-leaning
SaProt	LLR -12.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.41 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,920 alleles

Overall 6.2e-05% 1/1,614,036 alleles · very rare exomes 1/1,461,726 · genomes 0/152,310 · 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: B9D1
Protein: p.Pro142Ser
Coding: c.424C>T
MANE Select: NM_015681
Type: single nucleotide variant
Location: chr17:19343838 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.05

Full B9D1 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

B9D1 p.Ser142Ter Uncertain significance ★ same residue
B9D1 p.Pro142= Likely benign ★ same residue
B9D1 p.Ala44Val Uncertain significance ★★ ⚠ same condition
B9D1 p.Arg101Gln Uncertain significance ★★ same condition
B9D1 p.Arg140Gln Uncertain significance ★★ ⚠ same condition
B9D1 p.Asn14Ser Uncertain significance ★★ ⚠ same condition
B9D1 p.Gly195Val Uncertain significance ★★ ⚠ same condition
B9D1 p.Phe122Ser 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/b9d1-p-pro142ser (accessed [today's date]).

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