Is BPTF p.Arg68Ser (c.204G>C) pathogenic?

BPTF p.Arg68Ser (c.204G>C) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.6599); Ultra-rare (popmax 0.0267%, sas); Associated with Inborn genetic diseases.

How common is BPTF p.Arg68Ser (c.204G>C) in the general population?

BPTF p.Arg68Ser (c.204G>C) is ultra-rare (popmax 0.0267%, sas) (gnomAD).

What do computational predictors say about BPTF p.Arg68Ser (c.204G>C)?

AlphaMissense predicts likely pathogenic (score 0.6599) — an in-silico prediction, not a clinical call.

BPTF p.Arg68Ser

Q: What condition is associated with BPTF p.Arg68Ser (c.204G>C)?

BPTF p.Arg68Ser (c.204G>C) is associated with Inborn genetic diseases, Kaposi sarcoma, susceptibility to, neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

c.204G>C · VCV3481709

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6599 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6599	likely pathogenic
REVEL	0.049	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.34, phastCons 1
Regional constraint	o/e 1.43	unconstrained · MANE · 181 bp · p 0.00027 · regional, not allelic
Overall
CADD	16.63	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

Grpmax group 0.0267% South Asian · 6/22,430 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00158% 16/1,015,586 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0267%	3,738
Remaining individualsnot grpmax-eligible	0.00319%	31,360
European (non-Finnish)	0.00106%	94,612

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.Arg68Ser
Coding: c.204G>C
MANE Select: NM_182641
Type: single nucleotide variant
Location: chr17:67825928 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 68: the 'disordered' region

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: Kaposi sarcoma, susceptibility to neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Similar variants

BPTF p.Arg68Met Uncertain significance ★ same residue
BPTF p.Arg68Thr Uncertain significance ★ ⚠ same residue
BPTF p.Arg68fs Pathogenic ★ same residue
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

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-arg68ser (accessed [today's date]).

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