Is MRTFA p.Ser790Leu (c.2369C>T) pathogenic?

MRTFA p.Ser790Leu (c.2369C>T) is classified Conflicting classifications of pathogenicity in MRTFA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-23). AlphaMissense: likely benign (0.0562); Very rare (popmax 0.00242%, eas).

How common is MRTFA p.Ser790Leu (c.2369C>T) in the general population?

MRTFA p.Ser790Leu (c.2369C>T) is very rare (popmax 0.00242%, eas) (gnomAD).

What do computational predictors say about MRTFA p.Ser790Leu (c.2369C>T)?

AlphaMissense predicts likely benign (score 0.0562) — an in-silico prediction, not a clinical call.

MRTFA p.Ser790Leu

c.2369C>T · rs761948522 · VCV1682958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0562 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00242%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0562	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.76	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 0.25	GERP -4.2
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	3.556	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 S690L vs ClinVar S790L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00242% East Asian · 1/41,340 alleles

Filtering AF 0.000635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00049%

Overall 0.00104% 16/1,545,224 alleles · very rare exomes 14/1,394,598 · genomes 2/150,626 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00242%	41,340
Remaining individualsnot grpmax-eligible	0.0017%	58,866
South Asian	0.00115%	87,184
European (non-Finnish)	0.00114%	87,802

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.Ser790Leu
Coding: c.2369C>T
MANE Select: NM_020831
dbSNP: rs761948522
Type: single nucleotide variant
Location: chr22:40417489 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 690 UniProt numbering: the 'disordered' region

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

Similar variants

MRTFA p.Ser790= 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-ser790leu (accessed [today's date]).

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