Is MRTFA p.Val598Met (c.1792G>A) pathogenic?

MRTFA p.Val598Met (c.1792G>A) is classified Uncertain significance in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.2187); Ultra-rare (popmax 0.0839%, afr).

How common is MRTFA p.Val598Met (c.1792G>A) in the general population?

MRTFA p.Val598Met (c.1792G>A) is ultra-rare (popmax 0.0839%, afr) (gnomAD).

What do computational predictors say about MRTFA p.Val598Met (c.1792G>A)?

AlphaMissense predicts likely benign (score 0.2187) — an in-silico prediction, not a clinical call.

MRTFA p.Val598Met

c.1792G>A · rs199750225 · VCV1683038

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2187 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0839%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2187	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -9.28	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 3.3	GERP -0.19, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	19.4	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 V498M vs ClinVar V598M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0839% African / African-American · 63/75,054 alleles

Filtering AF 0.0673% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0613%

Overall 0.0309% 499/1,612,886 alleles · ultra-rare exomes 436/1,460,566 · genomes 63/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0839%	1,191
East Asian	0.0513%	1,951
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0312%	3,206
South Asian	0.022%	4,555
Remaining individualsnot grpmax-eligible	0.0208%	4,806
Admixed American	0.01%	10,001
Finnishnot grpmax-eligible	0.00636%	15,723

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.Val598Met
Coding: c.1792G>A
MANE Select: NM_020831
dbSNP: rs199750225
Type: single nucleotide variant
Location: chr22:40418946 (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.Val598Leu Uncertain significance ★ ⚠ same residue
MRTFA p.Val598= 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-val598met (accessed [today's date]).

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