Is BORCS7 p.His65Tyr (c.193C>T) pathogenic?

BORCS7 p.His65Tyr (c.193C>T) is classified Uncertain significance in BORCS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-18). AlphaMissense: ambiguous (0.4378); Ultra-rare (popmax 0.0317%, amr).

How common is BORCS7 p.His65Tyr (c.193C>T) in the general population?

BORCS7 p.His65Tyr (c.193C>T) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about BORCS7 p.His65Tyr (c.193C>T)?

AlphaMissense predicts ambiguous (score 0.4378) — an in-silico prediction, not a clinical call.

BORCS7 p.His65Tyr

c.193C>T · VCV3992411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4378 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4378	ambiguous
REVEL	0.189	benign-leaning
SaProt	LLR -7.70	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,634 bp · p 0.5 · regional, not allelic
Overall
CADD	24.4	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 0.0317% Admixed American · 19/59,962 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00118% 19/1,613,706 alleles · ultra-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: BORCS7
Protein: p.His65Tyr
Coding: c.193C>T
MANE Select: NM_001136200
Type: single nucleotide variant
Location: chr10:102860383 (GRCh38)
Gene constraint: LOEUF 1.484 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.84

Full BORCS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BORCS7 p.Arg44Gln Uncertain significance ★ ⚠ same type
BORCS7 p.Arg44Trp Uncertain significance ★ ⚠ same type
BORCS7 p.Gln10Arg Uncertain significance ★ ⚠ same type
BORCS7 p.Gln84Arg Uncertain significance ★ ⚠ same type
BORCS7 p.Gln88Glu Uncertain significance ★ ⚠ same type
BORCS7 p.Gln98Glu Uncertain significance ★ ⚠ same type
BORCS7 p.Glu8Gln Uncertain significance ★ ⚠ same type
BORCS7 p.Gly5Arg 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/borcs7-p-his65tyr (accessed [today's date]).

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