Is MRTFA p.Arg560= (c.1680C>T) pathogenic?

MRTFA p.Arg560= (c.1680C>T) is classified Likely benign in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-05). Very rare (popmax 0.00433%, nfe).

How common is MRTFA p.Arg560= (c.1680C>T) in the general population?

MRTFA p.Arg560= (c.1680C>T) is very rare (popmax 0.00433%, nfe) (gnomAD).

MRTFA p.Arg560=

c.1680C>T · rs375086868 · VCV1969457

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00433%, nfe)

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 0.29	GERP -5.1, phastCons 0.92
Overall
CADD	0.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00433% European (non-Finnish) · 51/1,178,994 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00342% 55/1,610,500 alleles · very rare exomes 54/1,458,376 · genomes 1/152,124 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00433%	23,118
Remaining individualsnot grpmax-eligible	0.00321%	31,182
African / African-American	0.00134%	74,850
South Asian	0.0011%	90,776

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.Arg560=
Coding: c.1680C>T
MANE Select: NM_020831
dbSNP: rs375086868
Type: single nucleotide variant
Location: chr22:40419058 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 560: the 'disordered' region

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

Similar variants

MRTFA p.Arg560His Uncertain significance ★★ ⚠ same residue
MRTFA p.Arg560Cys Uncertain significance ★ ⚠ 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-arg560 (accessed [today's date]).

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