Is BORA p.His77Arg (c.230A>G) pathogenic?

BORA p.His77Arg (c.230A>G) is classified Uncertain significance in BORA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: likely benign (0.1181); Very rare (popmax 0.00447%, eas).

How common is BORA p.His77Arg (c.230A>G) in the general population?

BORA p.His77Arg (c.230A>G) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about BORA p.His77Arg (c.230A>G)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

BORA p.His77Arg

c.230A>G · VCV3481564

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -4.97	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 8.1	GERP 1, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 26 kb · p 6.5e-05 · regional, not allelic
Overall
CADD	19.4	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 0.00447% East Asian · 2/44,776 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000248% 4/1,611,194 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,388
Admixed American	0.00334%	29,959

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: BORA
Protein: p.His77Arg
Coding: c.230A>G
MANE Select: NM_024808
Type: single nucleotide variant
Location: chr13:72731357 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.50

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

Similar variants

BORA p.Ala258Val Uncertain significance ★ ⚠ same type
BORA p.Ala40Thr Uncertain significance ★ ⚠ same type
BORA p.Ala40Val Uncertain significance ★ ⚠ same type
BORA p.Ala551Val Uncertain significance ★ ⚠ same type
BORA p.Arg317Gly Uncertain significance ★ ⚠ same type
BORA p.Arg386Trp Uncertain significance ★ ⚠ same type
BORA p.Arg78His Uncertain significance ★ ⚠ same type
BORA p.Asn492Ile 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/bora-p-his77arg (accessed [today's date]).

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