Is BORCS8 p.Glu27Lys (c.79G>A) pathogenic?

BORCS8 p.Glu27Lys (c.79G>A) is classified Uncertain significance in BORCS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely pathogenic (0.9982); Very rare (popmax 0.000349%, nfe).

How common is BORCS8 p.Glu27Lys (c.79G>A) in the general population?

BORCS8 p.Glu27Lys (c.79G>A) is very rare (popmax 0.000349%, nfe) (gnomAD).

What do computational predictors say about BORCS8 p.Glu27Lys (c.79G>A)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

BORCS8 p.Glu27Lys

c.79G>A · rs2060415315 · VCV2284294

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000349%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic · top 2% in BORCS8
REVEL	0.475	indeterminate
SaProt	LLR -6.57	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.96 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000349% European (non-Finnish) · 4/1,146,912 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000286% 4/1,399,074 alleles · very rare

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.Glu27Lys
Coding: c.79G>A
MANE Select: NM_001145784
dbSNP: rs2060415315
Type: single nucleotide variant
Location: chr19:19186964 (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-glu27lys (accessed [today's date]).

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