Is BGLAP p.Ala23Val (c.68C>T) pathogenic?

BGLAP p.Ala23Val (c.68C>T) is classified Uncertain significance in BGLAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.1044); Very rare (popmax 0.00821%, afr).

How common is BGLAP p.Ala23Val (c.68C>T) in the general population?

BGLAP p.Ala23Val (c.68C>T) is very rare (popmax 0.00821%, afr) (gnomAD).

What do computational predictors say about BGLAP p.Ala23Val (c.68C>T)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

BGLAP p.Ala23Val

c.68C>T · rs183196972 · VCV3133792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00821%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1044	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -9.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2, phastCons 0.99
Regional constraint	o/e 0.89	unconstrained · MANE · 927 bp · p 0.22 · regional, not allelic
Overall
CADD	12.66	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 0.00821% African / African-American · 6/73,104 alleles

Filtering AF 0.00354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.000709% 11/1,552,128 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00821%	12,184
Admixed American	0.00196%	51,036
Remaining individualsnot grpmax-eligible	0.00166%	60,148
South Asian	0.00119%	84,160
European (non-Finnish)	0.000174%	573,602

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.Ala23Val
Coding: c.68C>T
MANE Select: NM_199173
dbSNP: rs183196972
Type: single nucleotide variant
Location: chr1:156242556 (GRCh38)
Gene constraint: LOEUF 1.795 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.66 · 9 PDB

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

Similar variants

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
BGLAP p.Leu15Phe 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-ala23val (accessed [today's date]).

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