Is MRTFA p.Pro868= (c.2604G>A) pathogenic?

MRTFA p.Pro868= (c.2604G>A) is classified Likely benign in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-06). Very rare (popmax 0.00611%, nfe).

How common is MRTFA p.Pro868= (c.2604G>A) in the general population?

MRTFA p.Pro868= (c.2604G>A) is very rare (popmax 0.00611%, nfe) (gnomAD).

MRTFA p.Pro868=

c.2604G>A · rs754100449 · VCV1682936

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00611%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.057	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -2.9
Overall
CADD	6.759	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00611% European (non-Finnish) · 68/1,113,428 alleles

Filtering AF 0.00489% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00448%

Overall 0.00689% 102/1,479,700 alleles · very rare exomes 91/1,327,592 · genomes 11/152,108 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0338%	2,955
Remaining individualsnot grpmax-eligible	0.0212%	4,708
European (non-Finnish)grpmax	0.00611%	16,374
Admixed American	0.0049%	20,423

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro868=
Coding: c.2604G>A
MANE Select: NM_020831
dbSNP: rs754100449
Type: single nucleotide variant
Location: chr22:40411882 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 868: 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.Pro868Leu Uncertain significance ★★ ⚠ same residue
MRTFA p.Pro868Ser 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-pro868 (accessed [today's date]).

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