Is BMP8A p.Arg242Cys (c.724C>T) pathogenic?

BMP8A p.Arg242Cys (c.724C>T) is classified Uncertain significance in BMP8A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.1345); Ultra-rare (popmax 0.0221%, eas).

How common is BMP8A p.Arg242Cys (c.724C>T) in the general population?

BMP8A p.Arg242Cys (c.724C>T) is ultra-rare (popmax 0.0221%, eas) (gnomAD).

What do computational predictors say about BMP8A p.Arg242Cys (c.724C>T)?

AlphaMissense predicts likely benign (score 0.1345) — an in-silico prediction, not a clinical call.

BMP8A p.Arg242Cys

c.724C>T · VCV3481183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1345 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0221%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1345	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -8.10	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 1.2	GERP -3.7, phastCons 0.24
Regional constraint	o/e 0.02	constrained · MANE · 10 kb · p 9.1e-28 · regional, not allelic
Overall
CADD	23.9	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 0.0221% East Asian · 5/22,650 alleles

Filtering AF 0.00861% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00556%

Overall 0.00209% 26/1,241,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0221%	4,530
African / African-American	0.0115%	8,722
South Asian	0.00431%	23,180
European (non-Finnish)	0.00129%	77,714

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: BMP8A
Protein: p.Arg242Cys
Coding: c.724C>T
MANE Select: NM_181809
Type: single nucleotide variant
Location: chr1:39521426 (GRCh38)
Gene constraint: LOEUF 1.337 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.87

Full BMP8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BMP8A p.Ala144Val Uncertain significance ★★ ⚠ same type
BMP8A p.Arg293His Benign ★★ same type
BMP8A p.Ala102Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala201Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala264Thr Uncertain significance ★ ⚠ same type
BMP8A p.Ala348Val Uncertain significance ★ ⚠ same type
BMP8A p.Ala365Val Uncertain significance ★ ⚠ same type
BMP8A p.Ala374Thr 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/bmp8a-p-arg242cys (accessed [today's date]).

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