Is BPTF p.Glu554Val (c.1661A>T) pathogenic?

BPTF p.Glu554Val (c.1661A>T) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-20). AlphaMissense: likely pathogenic (0.7158); Very rare (popmax 0.00451%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Glu554Val (c.1661A>T)?

BPTF p.Glu554Val (c.1661A>T) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Glu554Val (c.1661A>T) in the general population?

BPTF p.Glu554Val (c.1661A>T) is very rare (popmax 0.00451%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Glu554Val (c.1661A>T)?

AlphaMissense predicts likely pathogenic (score 0.7158) — an in-silico prediction, not a clinical call.

BPTF p.Glu554Val

c.1661A>T · rs375245234 · VCV1699737

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7158 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00451%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7158	likely pathogenic
REVEL	0.156	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.38	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 37 kb · p 0.31 · regional, not allelic
Overall
CADD	34.0	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 0.00451% European (non-Finnish) · 53/1,175,520 alleles

Filtering AF 0.00352% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00319%

Overall 0.00374% 60/1,602,516 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00484%	20,645
European (non-Finnish)grpmax	0.00451%	22,180
African / African-American	0.00271%	36,948
Admixed American	0.00174%	57,386
South Asian	0.00112%	89,130

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.Glu554Val
Coding: c.1661A>T
MANE Select: NM_182641
dbSNP: rs375245234
Type: single nucleotide variant
Location: chr17:67874817 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1078Gln Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg215His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2352His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2858Gln Uncertain significance ★★ ⚠ same condition
BPTF p.Arg68Ser Uncertain significance ★★ ⚠ same condition

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-glu554val (accessed [today's date]).

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