Is BPTF p.Ser1623Ala (c.4867T>G) pathogenic?

BPTF p.Ser1623Ala (c.4867T>G) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-02). AlphaMissense: likely benign (0.1686); Ultra-rare (popmax 0.0155%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Ser1623Ala (c.4867T>G)?

BPTF p.Ser1623Ala (c.4867T>G) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Ser1623Ala (c.4867T>G) in the general population?

BPTF p.Ser1623Ala (c.4867T>G) is ultra-rare (popmax 0.0155%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Ser1623Ala (c.4867T>G)?

AlphaMissense predicts likely benign (score 0.1686) — an in-silico prediction, not a clinical call.

BPTF p.Ser1623Ala

c.4867T>G · rs147928104 · VCV2216352

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0155%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1686	likely benign
REVEL	0.174	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 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 443 bp · p 0.013 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S1749A vs ClinVar S1623A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0155% European (non-Finnish) · 183/1,179,994 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0129%

Overall 0.0117% 189/1,613,774 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0155%	6,448
African / African-American	0.00401%	24,953
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	59,992

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.Ser1623Ala
Coding: c.4867T>G
MANE Select: NM_182641
dbSNP: rs147928104
Type: single nucleotide variant
Location: chr17:67912751 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1623: 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.Ser1623Thr Uncertain significance ★ ⚠ same residue
BPTF p.Ser1623= Likely benign ★ 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

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-ser1623ala (accessed [today's date]).

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