Is BPTF p.Glu358Asp (c.1074G>C) pathogenic?

BPTF p.Glu358Asp (c.1074G>C) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-26). AlphaMissense: likely benign (0.1331); Ultra-rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Glu358Asp (c.1074G>C)?

BPTF p.Glu358Asp (c.1074G>C) is associated with Inborn genetic diseases, neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.Glu358Asp (c.1074G>C) in the general population?

BPTF p.Glu358Asp (c.1074G>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about BPTF p.Glu358Asp (c.1074G>C)?

AlphaMissense predicts likely benign (score 0.1331) — an in-silico prediction, not a clinical call.

BPTF p.Glu358Asp

c.1074G>C · rs991755344 · VCV1805684

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1331 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1331	likely benign
REVEL	0.104	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 512 bp · p 3.3e-14 · regional, not allelic
Overall
CADD	20.1	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 0.01% Admixed American · 6/59,990 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000743% 12/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	8.47e-05%	1,180,030

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.Glu358Asp
Coding: c.1074G>C
MANE Select: NM_182641
dbSNP: rs991755344
Type: single nucleotide variant
Location: chr17:67854400 (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

Also linked: neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Similar variants

BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ same condition
BPTF p.Arg2858Ter Pathogenic ★★ same condition
BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1078Gln Uncertain significance ★★ same condition
BPTF p.Arg2058Cys Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg215His 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-glu358asp (accessed [today's date]).

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