Is BPTF p.Pro1802Ala (c.5404C>G) pathogenic?

BPTF p.Pro1802Ala (c.5404C>G) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-12). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0165%, mid); Associated with syndromic intellectual disability.

What condition is associated with BPTF p.Pro1802Ala (c.5404C>G)?

BPTF p.Pro1802Ala (c.5404C>G) is associated with syndromic intellectual disability (ClinVar).

How common is BPTF p.Pro1802Ala (c.5404C>G) in the general population?

BPTF p.Pro1802Ala (c.5404C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BPTF p.Pro1802Ala (c.5404C>G)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

BPTF p.Pro1802Ala

c.5404C>G · VCV3261404

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

syndromic intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.09	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 6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 11 kb · p 2e-06 · regional, not allelic
Overall
CADD	21.7	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 P1928A vs ClinVar P1802A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000372% 6/1,613,418 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
European (non-Finnish)	0.000424%	235,934

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.Pro1802Ala
Coding: c.5404C>G
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67918814 (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

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

Similar variants

BPTF p.Arg1199Gly Uncertain significance ★ ⚠ same condition
BPTF p.Asp2509Val Uncertain significance ★ ⚠ same condition
BPTF p.Ile2473Val 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
BPTF p.Arg1322Ter Pathogenic/Likely pathogenic ★★ 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-pro1802ala (accessed [today's date]).

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