Is BORCS8 p.Arg85Leu (c.254G>T) pathogenic?

BORCS8 p.Arg85Leu (c.254G>T) is classified Uncertain significance in BORCS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1744); Very rare (popmax 0.00245%, eas).

How common is BORCS8 p.Arg85Leu (c.254G>T) in the general population?

BORCS8 p.Arg85Leu (c.254G>T) is very rare (popmax 0.00245%, eas) (gnomAD).

What do computational predictors say about BORCS8 p.Arg85Leu (c.254G>T)?

AlphaMissense predicts likely benign (score 0.1744) — an in-silico prediction, not a clinical call.

BORCS8 p.Arg85Leu

c.254G>T · rs897542083 · VCV3134785

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1744	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00245% East Asian · 1/40,898 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000286% 4/1,398,974 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00245%	40,898
Admixed American	0.00196%	50,982
European (non-Finnish)	0.000174%	573,441

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: BORCS8
Protein: p.Arg85Leu
Coding: c.254G>T
MANE Select: NM_001145784
dbSNP: rs897542083
Type: single nucleotide variant
Location: chr19:19182645 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.74

Full BORCS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS8 p.Arg85His Uncertain significance ★ ⚠ same residue
BORCS8 p.Glu68Ter Likely pathogenic ★ same type
BORCS8 p.Ala25Gly Uncertain significance ★ ⚠ same type
BORCS8 p.Arg40His Uncertain significance ★ ⚠ same type
BORCS8 p.Arg55Cys Uncertain significance ★ ⚠ same type
BORCS8 p.Arg55Leu Uncertain significance ★ ⚠ same type
BORCS8 p.Arg98Trp Uncertain significance ★ ⚠ same type
BORCS8 p.Gln54Pro Uncertain significance ★ same type

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/borcs8-p-arg85leu (accessed [today's date]).

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