Is BORCS8 p.Pro115Leu (c.344C>T) pathogenic?

BORCS8 p.Pro115Leu (c.344C>T) is classified Uncertain significance in BORCS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.0566); Rare (popmax 0.65%, eas).

How common is BORCS8 p.Pro115Leu (c.344C>T) in the general population?

BORCS8 p.Pro115Leu (c.344C>T) is rare (popmax 0.65%, eas) (gnomAD).

What do computational predictors say about BORCS8 p.Pro115Leu (c.344C>T)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

BORCS8 p.Pro115Leu

c.344C>T · VCV4646404

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.65%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -9.70	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 -1.1	GERP -2.1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	14.46	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 0.65% East Asian · 266/40,896 alleles

Filtering AF 0.586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.561%

Overall 0.0235% 364/1,549,680 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.65%	154
Remaining individualsnot grpmax-eligible	0.0133%	7,496
Finnishnot grpmax-eligible	0.00836%	11,960
European (non-Finnish)	0.00724%	13,810
African / African-American	0.00137%	73,100
South Asian	0.00119%	83,858

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.Pro115Leu
Coding: c.344C>T
MANE Select: NM_001145784
Type: single nucleotide variant
Location: chr19:19180744 (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.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.Arg85His Uncertain significance ★ ⚠ same type
BORCS8 p.Arg85Leu Uncertain significance ★ ⚠ same type
BORCS8 p.Arg98Trp 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-pro115leu (accessed [today's date]).

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