Is MRTFA p.Arg514Trp (c.1540C>T) pathogenic?

MRTFA p.Arg514Trp (c.1540C>T) is classified Uncertain significance in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-29). AlphaMissense: likely benign (0.24); Very rare (popmax 0.00404%, afr).

How common is MRTFA p.Arg514Trp (c.1540C>T) in the general population?

MRTFA p.Arg514Trp (c.1540C>T) is very rare (popmax 0.00404%, afr) (gnomAD).

What do computational predictors say about MRTFA p.Arg514Trp (c.1540C>T)?

AlphaMissense predicts likely benign (score 0.24) — an in-silico prediction, not a clinical call.

MRTFA p.Arg514Trp

c.1540C>T · rs1210675215 · VCV2994344

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.24 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00404%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.24	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R414W vs ClinVar R514W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00404% African / African-American · 3/74,272 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000543%

Overall 0.00113% 18/1,592,286 alleles · very rare exomes 14/1,440,090 · genomes 4/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00404%	24,757
Admixed American	0.00175%	56,992
European (non-Finnish)	0.0012%	83,537

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.Arg514Trp
Coding: c.1540C>T
MANE Select: NM_020831
dbSNP: rs1210675215
Type: single nucleotide variant
Location: chr22:40419198 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB

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

Similar variants

MRTFA p.Arg514Gln 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
MRTFA p.Ala537Val 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-arg514trp (accessed [today's date]).

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