Is MRTFB p.Thr9= (c.27C>T) pathogenic?

MRTFB p.Thr9= (c.27C>T) is classified Benign in MRTFB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-02). Rare (popmax 0.434%, nfe).

How common is MRTFB p.Thr9= (c.27C>T) in the general population?

MRTFB p.Thr9= (c.27C>T) is rare (popmax 0.434%, nfe) (gnomAD).

MRTFB p.Thr9=

c.27C>T · rs140275336 · VCV717395

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.434%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.4
Overall
CADD	4.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.434% European (non-Finnish) · 5,116/1,180,012 alleles

Filtering AF 0.424% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.42%

Overall 0.395% 6,371/1,614,112 alleles · rare exomes 5,850/1,461,878 · genomes 521/152,234 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	6.14%	16
Finnishnot grpmax-eligible	0.823%	121
Ashkenazi Jewishnot grpmax-eligible	0.476%	210
European (non-Finnish)grpmax	0.434%	231
Remaining individualsnot grpmax-eligible	0.302%	331
South Asian	0.242%	414
Middle Eastern	0.099%	1,010
Admixed American	0.0933%	1,072
African / African-American	0.08%	1,250

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr9=
Coding: c.27C>T
MANE Select: NM_001308142
dbSNP: rs140275336
Type: single nucleotide variant
Location: chr16:14140633 (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.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
MRTFB p.Ala17Thr 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-thr9 (accessed [today's date]).

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