Is BGLAP p.Phe36Ser (c.107T>C) pathogenic?

BGLAP p.Phe36Ser (c.107T>C) is classified Uncertain significance in BGLAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely pathogenic (0.6533); Very rare (popmax 0.00269%, afr).

How common is BGLAP p.Phe36Ser (c.107T>C) in the general population?

BGLAP p.Phe36Ser (c.107T>C) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about BGLAP p.Phe36Ser (c.107T>C)?

AlphaMissense predicts likely pathogenic (score 0.6533) — an in-silico prediction, not a clinical call.

BGLAP p.Phe36Ser

c.107T>C · VCV4206727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6533	likely pathogenic
REVEL	0.319	indeterminate
SaProt	LLR -2.69	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 927 bp · p 0.22 · regional, not allelic
Overall
CADD	25.2	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 0.00269% African / African-American · 2/74,482 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000125% 2/1,595,600 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.Phe36Ser
Coding: c.107T>C
MANE Select: NM_199173
Type: single nucleotide variant
Location: chr1:156242765 (GRCh38)
Gene constraint: LOEUF 1.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.66 · 9 PDB
Residue 36: a β-strand

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-phe36ser (accessed [today's date]).

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