Is BPTF p.Ser73Arg (c.219C>A) pathogenic?

BPTF p.Ser73Arg (c.219C>A) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-27). AlphaMissense: likely pathogenic (0.5963); Ultra-rare (popmax 0.048%, mid).

How common is BPTF p.Ser73Arg (c.219C>A) in the general population?

BPTF p.Ser73Arg (c.219C>A) is ultra-rare (popmax 0.048%, mid) (gnomAD).

What do computational predictors say about BPTF p.Ser73Arg (c.219C>A)?

AlphaMissense predicts likely pathogenic (score 0.5963) — an in-silico prediction, not a clinical call.

BPTF p.Ser73Arg

c.219C>A · VCV4760928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5963 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.048%, mid)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.5963	likely pathogenic
REVEL	0.054	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.25, phastCons 1
Regional constraint	o/e 1.43	unconstrained · MANE · 181 bp · p 0.00027 · regional, not allelic
Overall
CADD	15.03	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.048% Middle Eastern · 1/2,082 alleles

Filtering AF 0.00735% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00679%

Overall 0.0077% 78/1,013,602 alleles · ultra-rare exomes 75/866,404 · genomes 3/147,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.048%	2,082
European (non-Finnish)	0.00905%	11,044

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: BPTF
Protein: p.Ser73Arg
Coding: c.219C>A
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67825943 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 73: the 'disordered' region

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

Similar variants

BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ same type
BPTF p.Arg1738Ter Pathogenic/Likely pathogenic ★★ same type
BPTF p.Arg2858Ter Pathogenic ★★ same type
BPTF p.Arg841Ter Pathogenic ★★ same type
BPTF c.1864+562A>T Uncertain significance ★★ same type
BPTF c.1865-5651C>G Uncertain significance ★★ ⚠ same type
BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same type
BPTF p.Ala1252Val 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/bptf-p-ser73arg (accessed [today's date]).

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