Is BGLAP p.Pro60Ser (c.178C>T) pathogenic?

BGLAP p.Pro60Ser (c.178C>T) is classified Uncertain significance in BGLAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.077); Very rare (popmax 8.47e-05%, nfe).

How common is BGLAP p.Pro60Ser (c.178C>T) in the general population?

BGLAP p.Pro60Ser (c.178C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BGLAP p.Pro60Ser (c.178C>T)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

BGLAP p.Pro60Ser

c.178C>T · rs1156972711 · VCV3133791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.3	indeterminate
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.62, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 927 bp · p 0.22 · regional, not allelic
Overall
CADD	15.61	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.84e-05% 1/1,461,794 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: BGLAP
Protein: p.Pro60Ser
Coding: c.178C>T
MANE Select: NM_199173
dbSNP: rs1156972711
Type: single nucleotide variant
Location: chr1:156243037 (GRCh38)
Gene constraint: LOEUF 1.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.66 · 9 PDB
Residue 60: the gla domain; a functional site (not hydroxylated)

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

Similar variants

BGLAP p.Ala23Val Uncertain significance ★ ⚠ same type
BGLAP p.Arg94Trp Uncertain significance ★ ⚠ same type
BGLAP p.Asp81Glu Uncertain significance ★ ⚠ same type
BGLAP p.Asp85Gly Uncertain significance ★ ⚠ same type
BGLAP p.Gly27Ser Uncertain significance ★ ⚠ same type
BGLAP p.Gly88Ser Uncertain significance ★ ⚠ same type
BGLAP p.Gly98Ser Uncertain significance ★ ⚠ same type
BGLAP p.Ile87Met 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/bglap-p-pro60ser (accessed [today's date]).

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