Is MRTFA p.Ser592Pro (c.1774T>C) pathogenic?

MRTFA p.Ser592Pro (c.1774T>C) is classified Uncertain significance in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-15). AlphaMissense: likely benign (0.2879); Absent from gnomAD v4.1.

How common is MRTFA p.Ser592Pro (c.1774T>C) in the general population?

MRTFA p.Ser592Pro (c.1774T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MRTFA p.Ser592Pro (c.1774T>C)?

AlphaMissense predicts likely benign (score 0.2879) — an in-silico prediction, not a clinical call.

MRTFA p.Ser592Pro

c.1774T>C · rs2052759816 · VCV1904051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2879 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2879	likely benign
REVEL	0.322	indeterminate
SaProt	LLR -5.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	24.4	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 S492P vs ClinVar S592P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MRTFA
Protein: p.Ser592Pro
Coding: c.1774T>C
MANE Select: NM_020831
dbSNP: rs2052759816
Type: single nucleotide variant
Location: chr22:40418964 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 492 UniProt numbering: a modified residue (phosphoserine)

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

Similar variants

MRTFA p.Ser592= Likely benign ★★ same residue
MRTFA p.Ser592Leu 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-ser592pro (accessed [today's date]).

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