Is BPTF p.Tyr1708= (c.5124T>C) pathogenic?

BPTF p.Tyr1708= (c.5124T>C) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). Ultra-rare (popmax 0.0373%, afr).

How common is BPTF p.Tyr1708= (c.5124T>C) in the general population?

BPTF p.Tyr1708= (c.5124T>C) is ultra-rare (popmax 0.0373%, afr) (gnomAD).

BPTF p.Tyr1708=

c.5124T>C · rs112258244 · VCV1972457

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0373%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.06	GERP -4, phastCons 0.97
Overall
CADD	3.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0373% African / African-American · 28/75,054 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.00427% 69/1,614,180 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0576%	1,736
African / African-Americangrpmax	0.0373%	2,680
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,009
East Asian	0.00223%	44,888
European (non-Finnish)	8.47e-05%	1,180,027

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr1708=
Coding: c.5124T>C
MANE Select: NM_182641
dbSNP: rs112258244
Type: single nucleotide variant
Location: chr17:67913008 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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-tyr1708 (accessed [today's date]).

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