Is BPTF p.Arg2058His (c.6173G>A) pathogenic?

BPTF p.Arg2058His (c.6173G>A) is classified Likely benign in BPTF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.3202); Ultra-rare (popmax 0.0264%, sas); Associated with Inborn genetic diseases.

What condition is associated with BPTF p.Arg2058His (c.6173G>A)?

BPTF p.Arg2058His (c.6173G>A) is associated with Inborn genetic diseases (ClinVar).

How common is BPTF p.Arg2058His (c.6173G>A) in the general population?

BPTF p.Arg2058His (c.6173G>A) is ultra-rare (popmax 0.0264%, sas) (gnomAD).

What do computational predictors say about BPTF p.Arg2058His (c.6173G>A)?

AlphaMissense predicts likely benign (score 0.3202) — an in-silico prediction, not a clinical call.

BPTF p.Arg2058His

c.6173G>A · rs552529693 · VCV3134904

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3202 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3202	likely benign
REVEL	0.176	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 8.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 18 kb · p 0.012 · regional, not allelic
Overall
CADD	24.9	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 R2184H vs ClinVar R2058H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0264% South Asian · 24/90,968 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.00198% 32/1,613,486 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0264%	3,790
East Asian	0.00446%	22,428
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.000339%	294,961

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.Arg2058His
Coding: c.6173G>A
MANE Select: NM_182641
dbSNP: rs552529693
Type: single nucleotide variant
Location: chr17:67931933 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2058: 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.Arg2058Cys 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-arg2058his (accessed [today's date]).

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