Is MRTFA p.Pro736= (c.2208C>T) pathogenic?

MRTFA p.Pro736= (c.2208C>T) is classified Likely benign in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-29). Ultra-rare (popmax 0.0508%, mid).

How common is MRTFA p.Pro736= (c.2208C>T) in the general population?

MRTFA p.Pro736= (c.2208C>T) is ultra-rare (popmax 0.0508%, mid) (gnomAD).

MRTFA p.Pro736=

c.2208C>T · rs746103537 · VCV1682983

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0508%, mid)

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 -8.4	GERP -4.7
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0508% Middle Eastern · 3/5,904 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00737%

Overall 0.00208% 33/1,587,462 alleles · ultra-rare exomes 28/1,435,206 · genomes 5/152,256 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0508%	1,968
Ashkenazi Jewishnot grpmax-eligible	0.00363%	27,554
European (non-Finnish)	0.00222%	45,051
Remaining individualsnot grpmax-eligible	0.00163%	61,226
Finnishnot grpmax-eligible	0.00159%	63,074
African / African-American	0.00136%	73,720

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.Pro736=
Coding: c.2208C>T
MANE Select: NM_020831
dbSNP: rs746103537
Type: single nucleotide variant
Location: chr22:40418530 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 736: the 'disordered' region; 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.Pro736Ser Uncertain significance ★★ ⚠ same residue
MRTFA p.Pro736Ala 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-pro736 (accessed [today's date]).

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