Is MYB p.Arg757= (c.2271G>A) pathogenic?

MYB p.Arg757= (c.2271G>A) is classified Benign in MYB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-07). Low-frequency (popmax 3.11%, nfe); Associated with MYB-related disorder.

What condition is associated with MYB p.Arg757= (c.2271G>A)?

MYB p.Arg757= (c.2271G>A) is associated with MYB-related disorder (ClinVar).

How common is MYB p.Arg757= (c.2271G>A) in the general population?

MYB p.Arg757= (c.2271G>A) is low-frequency (popmax 3.11%, nfe) (gnomAD).

MYB p.Arg757=

c.2271G>A · rs35664708 · VCV3037450

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.11%, nfe)

Conditions

MYB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.5, phastCons 1
Overall
CADD	7.302	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.11% European (non-Finnish) · 36,521/1,173,966 alleles

Filtering AF 3.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.07%

Overall 2.75% 44,224/1,607,410 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	6.72%	15
European (non-Finnish)grpmax	3.11%	32
Remaining individualsnot grpmax-eligible	2.32%	43
Admixed American	0.982%	102
Ashkenazi Jewishnot grpmax-eligible	0.92%	109
South Asian	0.791%	126
African / African-American	0.47%	213
Amishnot grpmax-eligible	0.439%	228
Middle Eastern	0.364%	275
East Asian	0.00223%	44,832

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MYB
Protein: p.Arg757=
Coding: c.2271G>A
MANE Select: NM_001130173
dbSNP: rs35664708
Type: single nucleotide variant
Location: chr6:135217965 (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

Disease context

MYB-related disorder

Similar variants

MYB p.Arg757Gln Uncertain significance ★ ⚠ same residue
MYB p.Glu629Ala Likely benign same condition
MYB p.Gly631Glu Likely benign same condition
MYB p.Pro361= Likely benign same condition
MYB p.Tyr110= Likely benign same condition
MYB p.Asp178fs Uncertain significance ★ same condition
MYB p.Thr589= Benign/Likely benign ★★ same type
MYB p.Ala278Thr 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-arg757 (accessed [today's date]).

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