Is BPTF p.Arg475Gln (c.1424G>A) pathogenic?

BPTF p.Arg475Gln (c.1424G>A) is classified Conflicting classifications of pathogenicity in BPTF (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-05-25). AlphaMissense: likely pathogenic (0.9743); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

What condition is associated with BPTF p.Arg475Gln (c.1424G>A)?

BPTF p.Arg475Gln (c.1424G>A) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.Arg475Gln (c.1424G>A) in the general population?

BPTF p.Arg475Gln (c.1424G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPTF p.Arg475Gln (c.1424G>A)?

AlphaMissense predicts likely pathogenic (score 0.9743) — an in-silico prediction, not a clinical call.

BPTF p.Arg475Gln

c.1424G>A · rs2510102579 · VCV1709195

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9743 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Computational evidence

Protein change
AlphaMissense	0.9743	likely pathogenic
REVEL	0.693	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 237 bp · p 2.2e-14 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BPTF
Protein: p.Arg475Gln
Coding: c.1424G>A
MANE Select: NM_182641
dbSNP: rs2510102579
Type: single nucleotide variant
Location: chr17:67854750 (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

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ same condition
BPTF p.Arg2858Ter Pathogenic ★★ same condition
BPTF p.Arg2058Cys Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2858Gln Uncertain significance ★★ ⚠ same condition
BPTF p.Arg542Gln Uncertain significance ★★ same condition
BPTF p.Arg68Ser Uncertain significance ★★ ⚠ same condition
BPTF p.Asn452Ser 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-arg475gln (accessed [today's date]).

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