Is MRTFA p.Glu247Lys (c.739G>A) pathogenic?

MRTFA p.Glu247Lys (c.739G>A) is classified Conflicting classifications of pathogenicity in MRTFA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-24). AlphaMissense: likely benign (0.1593); Rare (popmax 0.154%, amr).

How common is MRTFA p.Glu247Lys (c.739G>A) in the general population?

MRTFA p.Glu247Lys (c.739G>A) is rare (popmax 0.154%, amr) (gnomAD).

What do computational predictors say about MRTFA p.Glu247Lys (c.739G>A)?

AlphaMissense predicts likely benign (score 0.1593) — an in-silico prediction, not a clinical call.

MRTFA p.Glu247Lys

c.739G>A · rs200627669 · VCV1683149

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1593 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.154%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1593	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	25.7	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 E147K vs ClinVar E247K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.154% Admixed American · 89/57,656 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.119%

Overall 0.00641% 103/1,606,716 alleles · rare exomes 91/1,454,376 · genomes 12/152,340 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.154%	648
Remaining individualsnot grpmax-eligible	0.00322%	31,058
East Asian	0.00224%	44,600
South Asian	0.00222%	45,020
African / African-American	0.00134%	74,626
European (non-Finnish)	0.000679%	147,211

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.Glu247Lys
Coding: c.739G>A
MANE Select: NM_020831
dbSNP: rs200627669
Type: single nucleotide variant
Location: chr22:40424244 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 147 UniProt numbering: the 'mediates interaction with scai and actb' region; the 'disordered' region

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

Similar variants

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
MRTFA p.Ala616Val 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-glu247lys (accessed [today's date]).

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