Is MYB p.Arg4Ser (c.12A>C) pathogenic?

MYB p.Arg4Ser (c.12A>C) is classified Uncertain significance in MYB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely pathogenic (0.9869); Absent from gnomAD v4.1.

How common is MYB p.Arg4Ser (c.12A>C) in the general population?

MYB p.Arg4Ser (c.12A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYB p.Arg4Ser (c.12A>C)?

AlphaMissense predicts likely pathogenic (score 0.9869) — an in-silico prediction, not a clinical call.

MYB p.Arg4Ser

c.12A>C · rs2128277525 · VCV2236319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9869 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9869	likely pathogenic
REVEL	0.135	moderately benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 8,657 bp · p 1.8e-06 · regional, not allelic
Overall
CADD	28.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYB
Protein: p.Arg4Ser
Coding: c.12A>C
MANE Select: NM_001130173
dbSNP: rs2128277525
Type: single nucleotide variant
Location: chr6:135181525 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 59.16

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

Similar variants

MYB p.Thr589= Benign/Likely benign ★★ same type
MYB p.Ala278Thr Uncertain significance ★ ⚠ same type
MYB p.Ala470Ser Uncertain significance ★ same type
MYB p.Ala491Asp Uncertain significance ★ same type
MYB p.Ala719Glu Uncertain significance ★ ⚠ same type
MYB p.Arg337Gly Uncertain significance ★ ⚠ same type
MYB p.Arg484Trp Uncertain significance ★ same type
MYB p.Arg510Cys 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/myb-p-arg4ser (accessed [today's date]).

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