Is BPTF p.Ser2107Phe (c.6320C>T) pathogenic?

BPTF p.Ser2107Phe (c.6320C>T) is classified Uncertain significance in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-05). AlphaMissense: likely benign (0.2278); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

What condition is associated with BPTF p.Ser2107Phe (c.6320C>T)?

BPTF p.Ser2107Phe (c.6320C>T) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

How common is BPTF p.Ser2107Phe (c.6320C>T) in the general population?

BPTF p.Ser2107Phe (c.6320C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BPTF p.Ser2107Phe (c.6320C>T)?

AlphaMissense predicts likely benign (score 0.2278) — an in-silico prediction, not a clinical call.

BPTF p.Ser2107Phe

c.6320C>T · VCV4883351

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Computational evidence

Protein change
AlphaMissense	0.2278	likely benign
REVEL	0.431	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S2233F vs ClinVar S2107F) — verify the residue.

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.Ser2107Phe
Coding: c.6320C>T
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67940499 (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-ser2107phe (accessed [today's date]).

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