Is MRTFA p.Arg560His (c.1679G>A) pathogenic?

MRTFA p.Arg560His (c.1679G>A) is classified Uncertain significance in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-27). AlphaMissense: likely benign (0.0945); Ultra-rare (popmax 0.054%, sas).

How common is MRTFA p.Arg560His (c.1679G>A) in the general population?

MRTFA p.Arg560His (c.1679G>A) is ultra-rare (popmax 0.054%, sas) (gnomAD).

What do computational predictors say about MRTFA p.Arg560His (c.1679G>A)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

MRTFA p.Arg560His

c.1679G>A · rs140573764 · VCV1000907

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.054%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 0.38, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	22.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R460H vs ClinVar R560H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.054% South Asian · 49/90,748 alleles

Filtering AF 0.0419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0376%

Overall 0.0179% 289/1,610,092 alleles · ultra-rare exomes 261/1,458,108 · genomes 28/151,984 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.054%	1,852
Middle Eastern	0.0329%	3,042
Admixed American	0.0235%	4,260
European (non-Finnish)	0.0168%	5,954
Remaining individualsnot grpmax-eligible	0.016%	6,236
African / African-American	0.0147%	6,797
East Asian	0.0067%	14,918
Finnishnot grpmax-eligible	0.0032%	31,226

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: MRTFA
Protein: p.Arg560His
Coding: c.1679G>A
MANE Select: NM_020831
dbSNP: rs140573764
Type: single nucleotide variant
Location: chr22:40419059 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 460 UniProt numbering: the 'disordered' region

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

Similar variants

MRTFA p.Arg560Cys Uncertain significance ★ ⚠ same residue
MRTFA p.Arg560= Likely benign ★ same residue
MRTFA p.Ala352Thr Uncertain significance ★★ ⚠ same type
MRTFA p.Ala360Thr Uncertain significance ★★ ⚠ same type
MRTFA p.Ala429Ser Uncertain significance ★★ ⚠ same type
MRTFA p.Ala479Gly Uncertain significance ★★ ⚠ same type
MRTFA p.Ala479Val Uncertain significance ★★ ⚠ same type
MRTFA p.Ala534Thr 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/mrtfa-p-arg560his (accessed [today's date]).

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