Is MRTFA p.Pro551Ser (c.1651C>T) pathogenic?

MRTFA p.Pro551Ser (c.1651C>T) is classified Uncertain significance in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). AlphaMissense: likely pathogenic (0.7379); Ultra-rare (popmax 0.0136%, amr).

How common is MRTFA p.Pro551Ser (c.1651C>T) in the general population?

MRTFA p.Pro551Ser (c.1651C>T) is ultra-rare (popmax 0.0136%, amr) (gnomAD).

What do computational predictors say about MRTFA p.Pro551Ser (c.1651C>T)?

AlphaMissense predicts likely pathogenic (score 0.7379) — an in-silico prediction, not a clinical call.

MRTFA p.Pro551Ser

c.1651C>T · rs752603698 · VCV1683060

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7379 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7379	likely pathogenic
REVEL	0.33	indeterminate
SaProt	LLR -8.35	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	25.3	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 P451S vs ClinVar P551S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% Admixed American · 8/58,748 alleles

Filtering AF 0.00684% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00528%

Overall 0.00649% 104/1,603,322 alleles · ultra-rare exomes 95/1,451,188 · genomes 9/152,134 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0136%	7,343
South Asian	0.0122%	8,177
Remaining individualsnot grpmax-eligible	0.00806%	12,403
European (non-Finnish)	0.00655%	15,268
East Asian	0.00226%	44,330
Finnishnot grpmax-eligible	0.00162%	61,828
African / African-American	0.00134%	74,474

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.Pro551Ser
Coding: c.1651C>T
MANE Select: NM_020831
dbSNP: rs752603698
Type: single nucleotide variant
Location: chr22:40419087 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 451 UniProt numbering: the 'disordered' region

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

Similar variants

MRTFA p.Pro551= Benign/Likely benign ★★ same residue
MRTFA p.Pro551Ala Uncertain significance ★ same residue
MRTFA p.Pro551Leu 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

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-pro551ser (accessed [today's date]).

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