Is BPTF p.Pro12= (c.36C>G) pathogenic?

BPTF p.Pro12= (c.36C>G) is classified Benign/Likely benign in BPTF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Common (popmax 7.91%, afr) — too common for a highly-penetrant pathogenic allele; Associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies.

BPTF p.Pro12=

Q: What condition is associated with BPTF p.Pro12= (c.36C>G)?

BPTF p.Pro12= (c.36C>G) is associated with neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (ClinVar).

Q: How common is BPTF p.Pro12= (c.36C>G) in the general population?

BPTF p.Pro12= (c.36C>G) is common (popmax 7.91%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.36C>G · rs868242186 · VCV1290490

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 7.91%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -0.39, phastCons 1
Overall
CADD	9.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.91% African / African-American · 4,600/58,146 alleles

Filtering AF 7.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.64%

Overall 0.479% 5,017/1,046,566 alleles · common exomes 1,670/898,512 · genomes 3,347/148,054 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.91%	13
Admixed American	0.848%	118
Remaining individualsnot grpmax-eligible	0.486%	206
Ashkenazi Jewishnot grpmax-eligible	0.125%	799
Middle Eastern	0.0893%	1,120
South Asian	0.0263%	3,804
European (non-Finnish)	0.00941%	10,630

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.Pro12=
Coding: c.36C>G
MANE Select: NM_182641
dbSNP: rs868242186
Type: single nucleotide variant
Location: chr17:67825760 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 12: the 'disordered' region

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-pro12 (accessed [today's date]).

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