Is MRTFA p.Pro886= (c.2658C>A) pathogenic?

MRTFA p.Pro886= (c.2658C>A) is classified Likely benign in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). Ultra-rare (popmax 0.0178%, mid).

How common is MRTFA p.Pro886= (c.2658C>A) in the general population?

MRTFA p.Pro886= (c.2658C>A) is ultra-rare (popmax 0.0178%, mid) (gnomAD).

MRTFA p.Pro886=

c.2658C>A · rs745413434 · VCV1682932

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.074	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -4.5
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% Middle Eastern · 1/5,618 alleles

Filtering AF 0.00344% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00299%

Overall 0.00377% 57/1,513,490 alleles · ultra-rare exomes 51/1,361,326 · genomes 6/152,164 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0178%	5,618
South Asian	0.00793%	12,618
European (non-Finnish)	0.00434%	23,020
African / African-American	0.00139%	71,884

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.Pro886=
Coding: c.2658C>A
MANE Select: NM_020831
dbSNP: rs745413434
Type: single nucleotide variant
Location: chr22:40411828 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 886: a UniProt-annotated variant site (in imd66; probable loss-of-function; patient's dendritic cells are morphologically distinct from control dendritic cells and show reduced spreading on fibronectin-coated coverslips, a marked reduction in total f-actin staining and a complete absence of podosomes, a similar phenotype to that of thp1 cells in which mrtfa was silenced)

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

Similar variants

MRTFA p.Pro886Arg Uncertain significance ★ ⚠ same residue
MRTFA p.Pro886Leu 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
MRTFA p.Ala534Thr 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-pro886 (accessed [today's date]).

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