Is BPTF p.Ser71Arg (c.211A>C) pathogenic?

BPTF p.Ser71Arg (c.211A>C) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-01). AlphaMissense: likely pathogenic (0.6838); Very rare (popmax 0.000118%, nfe).

How common is BPTF p.Ser71Arg (c.211A>C) in the general population?

BPTF p.Ser71Arg (c.211A>C) is very rare (popmax 0.000118%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Ser71Arg (c.211A>C)?

AlphaMissense predicts likely pathogenic (score 0.6838) — an in-silico prediction, not a clinical call.

BPTF p.Ser71Arg

c.211A>C · rs2055956220 · VCV2648122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000118%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6838	likely pathogenic
REVEL	0.08	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -0.68, phastCons 0.74
Regional constraint	o/e 1.43	unconstrained · MANE · 181 bp · p 0.00027 · regional, not allelic
Overall
CADD	15.39	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 0.000118% European (non-Finnish) · 1/849,480 alleles

Overall 0.000116% 1/865,218 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: BPTF
Protein: p.Ser71Arg
Coding: c.211A>C
MANE Select: NM_182641
dbSNP: rs2055956220
Type: single nucleotide variant
Location: chr17:67825935 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 71: the 'disordered' region

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

Similar variants

BPTF p.Ser71fs Pathogenic ★★ same residue
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

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-ser71arg (accessed [today's date]).

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