Is MRTFA p.Pro551= (c.1653C>G) pathogenic?

MRTFA p.Pro551= (c.1653C>G) is classified Benign/Likely benign in MRTFA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 63.9%, afr) — too common for a highly-penetrant pathogenic allele.

MRTFA p.Pro551=

Q: How common is MRTFA p.Pro551= (c.1653C>G) in the general population?

MRTFA p.Pro551= (c.1653C>G) is common (popmax 63.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1653C>G · rs8135911 · VCV1169626

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 63.9%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.5	GERP -4.9, phastCons 0.99
Overall
CADD	0.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.9% African / African-American · 47,622/74,484 alleles

Filtering AF 63.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 63.3%

Overall 3.89% 62,379/1,603,992 alleles · common exomes 34,101/1,451,908 · genomes 28,278/152,084 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	63.9%	2
Middle Eastern	9.88%	10
Ashkenazi Jewishnot grpmax-eligible	6.24%	16
Remaining individualsnot grpmax-eligible	5.59%	18
Admixed American	5.16%	19
South Asian	0.589%	170
European (non-Finnish)	0.449%	223
Amishnot grpmax-eligible	0.219%	456
Finnishnot grpmax-eligible	0.0161%	6,193

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.Pro551=
Coding: c.1653C>G
MANE Select: NM_020831
dbSNP: rs8135911
Type: single nucleotide variant
Location: chr22:40419085 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB

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

Similar variants

MRTFA p.Pro551Ser Uncertain significance ★★ ⚠ 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-pro551 (accessed [today's date]).

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