Is BPTF p.Ile2473Val (c.7417A>G) pathogenic?

BPTF p.Ile2473Val (c.7417A>G) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.088); Very rare (popmax 8.47e-05%, nfe); Associated with syndromic intellectual disability.

What condition is associated with BPTF p.Ile2473Val (c.7417A>G)?

BPTF p.Ile2473Val (c.7417A>G) is associated with syndromic intellectual disability (ClinVar).

How common is BPTF p.Ile2473Val (c.7417A>G) in the general population?

BPTF p.Ile2473Val (c.7417A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Ile2473Val (c.7417A>G)?

AlphaMissense predicts likely benign (score 0.088) — an in-silico prediction, not a clinical call.

BPTF p.Ile2473Val

c.7417A>G · VCV3778910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.088 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

syndromic intellectual disability

Computational evidence

Protein change
AlphaMissense	0.088	likely benign
REVEL	0.049	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 0.4	GERP -4.8, phastCons 0.004
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	7.52	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I2599V vs ClinVar I2473V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,892 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.Ile2473Val
Coding: c.7417A>G
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67946125 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2473: the 'disordered' region

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

Disease context

syndromic intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Ile2473= Likely benign ★ same residue
BPTF p.Pro1802Ala Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1199Gly Uncertain significance ★ ⚠ same condition
BPTF p.Asp2509Val Uncertain significance ★ same condition
BPTF p.Lys398Arg Conflicting classifications of pathogenicity ★ same condition
BPTF p.Lys546Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
BPTF p.Pro615Ala Uncertain significance ★ ⚠ same condition
BPTF p.Pro2677_Pro2678insAlaAlaProProAlaPro 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-ile2473val (accessed [today's date]).

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