Is BORA p.Arg78His (c.233G>A) pathogenic?

BORA p.Arg78His (c.233G>A) is classified Uncertain significance in BORA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.1791); Ultra-rare (popmax 0.0201%, eas).

How common is BORA p.Arg78His (c.233G>A) in the general population?

BORA p.Arg78His (c.233G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about BORA p.Arg78His (c.233G>A)?

AlphaMissense predicts likely benign (score 0.1791) — an in-silico prediction, not a clinical call.

BORA p.Arg78His

c.233G>A · rs374732607 · VCV2213684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1791 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1791	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -8.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 26 kb · p 6.5e-05 · regional, not allelic
Overall
CADD	29.7	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 0.0201% East Asian · 9/44,718 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00782%

Overall 0.00161% 26/1,610,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,969
African / African-American	0.00803%	12,450
South Asian	0.0011%	90,744
European (non-Finnish)	0.000849%	117,738

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.Arg78His
Coding: c.233G>A
MANE Select: NM_024808
dbSNP: rs374732607
Type: single nucleotide variant
Location: chr13:72731360 (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.Asn492Ile Uncertain significance ★ ⚠ same type
BORA p.Asp301Gly 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-arg78his (accessed [today's date]).

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