Is MRTFA p.Pro716= (c.2148G>A) pathogenic?

MRTFA p.Pro716= (c.2148G>A) is classified Benign/Likely benign in MRTFA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). Common (popmax 33.6%, afr) — too common for a highly-penetrant pathogenic allele.

MRTFA p.Pro716=

Q: How common is MRTFA p.Pro716= (c.2148G>A) in the general population?

MRTFA p.Pro716= (c.2148G>A) is common (popmax 33.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2148G>A · rs56211152 · VCV1165222

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 33.6%, 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 -3.2	GERP -4.7
Overall
CADD	0.585	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.6% African / African-American · 24,324/72,418 alleles

Filtering AF 33.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.1%

Overall 18.7% 288,739/1,546,306 alleles · common exomes 255,624/1,394,378 · genomes 33,115/151,928 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.6%	3
South Asian	26%	4
Middle Eastern	24%	4
Finnishnot grpmax-eligible	21.5%	5
Amishnot grpmax-eligible	19.1%	5
Remaining individualsnot grpmax-eligible	18.4%	5
European (non-Finnish)	18%	6
Ashkenazi Jewishnot grpmax-eligible	13.3%	8
Admixed American	11.5%	9
East Asian	6.14%	16

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.Pro716=
Coding: c.2148G>A
MANE Select: NM_020831
dbSNP: rs56211152
Type: single nucleotide variant
Location: chr22:40418590 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 716: the 'disordered' region

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

Similar variants

MRTFA p.Pro716Leu Conflicting classifications of pathogenicity ★ ⚠ 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
MRTFA p.Ala534Thr Uncertain significance ★★ ⚠ same type
MRTFA p.Ala537Val 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-pro716 (accessed [today's date]).

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