Is MRTFB p.Pro826Ser (c.2476C>T) pathogenic?

MRTFB p.Pro826Ser (c.2476C>T) is classified Uncertain significance in MRTFB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). Very rare (popmax 0.00133%, afr).

How common is MRTFB p.Pro826Ser (c.2476C>T) in the general population?

MRTFB p.Pro826Ser (c.2476C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

MRTFB p.Pro826Ser

c.2476C>T · VCV3913441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.037	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.34, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 43 kb · p 0.71 · regional, not allelic
Overall
CADD	17.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,936 alleles

Overall 6.2e-05% 1/1,614,054 alleles · very rare exomes 0/1,461,858 · genomes 1/152,196 · joint denominator

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: MRTFB
Protein: p.Pro826Ser
Coding: c.2476C>T
MANE Select: NM_001308142
Type: single nucleotide variant
Location: chr16:14251934 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 53.38

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-pro826ser (accessed [today's date]).

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