Is BPTF p.Gly49Ser (c.145G>A) pathogenic?

BPTF p.Gly49Ser (c.145G>A) is classified Uncertain significance in BPTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-13). AlphaMissense: likely pathogenic (0.7136); Very rare (popmax 0.00588%, amr); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Gly49Ser (c.145G>A)?

BPTF p.Gly49Ser (c.145G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Gly49Ser (c.145G>A) in the general population?

BPTF p.Gly49Ser (c.145G>A) is very rare (popmax 0.00588%, amr) (gnomAD).

What do computational predictors say about BPTF p.Gly49Ser (c.145G>A)?

AlphaMissense predicts likely pathogenic (score 0.7136) — an in-silico prediction, not a clinical call.

BPTF p.Gly49Ser

c.145G>A · rs1055623449 · VCV1977352

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00588%, amr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7136	likely pathogenic
REVEL	0.196	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 9.2	GERP 0.34, phastCons 1
Regional constraint	o/e 1.43	unconstrained · MANE · 181 bp · p 0.00027 · regional, not allelic
Overall
CADD	22.9	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 0.00588% Admixed American · 1/17,004 alleles

Overall 0.00204% 3/147,360 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00588%	17,004
Remaining individualsnot grpmax-eligible	0.0032%	31,268
African / African-American	0.00174%	57,356

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.Gly49Ser
Coding: c.145G>A
MANE Select: NM_182641
dbSNP: rs1055623449
Type: single nucleotide variant
Location: chr17:67825869 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 49: 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

Similar variants

BPTF p.Gly49Ala Uncertain significance ★ ⚠ same residue
BPTF p.Ala1197Val Uncertain significance ★★ ⚠ same condition
BPTF p.Ala1252Val Uncertain significance ★★ ⚠ same condition
BPTF p.Arg1078Gln Uncertain significance ★★ same condition
BPTF p.Arg2139His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg215His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2352His Uncertain significance ★★ ⚠ same condition
BPTF p.Arg2858Gln 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-gly49ser (accessed [today's date]).

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