Is MRTFB p.Ser477Ala (c.1429T>G) pathogenic?

MRTFB p.Ser477Ala (c.1429T>G) is classified Uncertain significance in MRTFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). Absent from gnomAD v4.1.

How common is MRTFB p.Ser477Ala (c.1429T>G) in the general population?

MRTFB p.Ser477Ala (c.1429T>G) is absent from gnomAD v4.1 (gnomAD).

MRTFB p.Ser477Ala

c.1429T>G · VCV4553418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.098	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.71	GERP -4.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 43 kb · p 0.71 · regional, not allelic
Overall
CADD	11.32	PHRED · no single calibrated threshold — expert panels disagree

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: MRTFB
Protein: p.Ser477Ala
Coding: c.1429T>G
MANE Select: NM_001308142
Type: single nucleotide variant
Location: chr16:14246689 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.38
Residue 477: the 'disordered' region

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

Similar variants

MRTFB p.Asn47= Benign/Likely benign ★★ same type
MRTFB p.Ser643= Benign ★★ same type
MRTFB p.Thr9= Benign ★★ same type
MRTFB p.Ala91Pro Pathogenic ★ same type
MRTFB p.Leu160Pro Likely pathogenic ★ same type
MRTFB c.693+1G>T Uncertain significance ★ same type
MRTFB p.Ala1080Val Uncertain significance ★ same type
MRTFB p.Ala138Glu 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/mrtfb-p-ser477ala (accessed [today's date]).

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