Is BPTF p.Ser2120Arg (c.6360C>G) pathogenic?

BPTF p.Ser2120Arg (c.6360C>G) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: ambiguous (0.3767); Very rare (popmax 0.000593%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Ser2120Arg (c.6360C>G)?

BPTF p.Ser2120Arg (c.6360C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Ser2120Arg (c.6360C>G) in the general population?

BPTF p.Ser2120Arg (c.6360C>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about BPTF p.Ser2120Arg (c.6360C>G)?

AlphaMissense predicts ambiguous (score 0.3767) — an in-silico prediction, not a clinical call.

BPTF p.Ser2120Arg

c.6360C>G · rs375577789 · VCV2507475

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3767	ambiguous
REVEL	0.059	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.079	GERP -4.8
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	13.92	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 S2246R vs ClinVar S2120R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,028 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00409% 66/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
Remaining individualsnot grpmax-eligible	0.0176%	5,681
European (non-Finnish)grpmax	0.000593%	168,576

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser2120Arg
Coding: c.6360C>G
MANE Select: NM_182641
dbSNP: rs375577789
Type: single nucleotide variant
Location: chr17:67940539 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BPTF p.Ser2120Asn 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-ser2120arg (accessed [today's date]).

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