Is MRTFA p.Ala737= (c.2211C>T) pathogenic?

MRTFA p.Ala737= (c.2211C>T) is classified Likely benign in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). Very rare (popmax 8.54e-05%, nfe).

How common is MRTFA p.Ala737= (c.2211C>T) in the general population?

MRTFA p.Ala737= (c.2211C>T) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

MRTFA p.Ala737=

c.2211C>T · rs1281698349 · VCV2741270

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

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 -0.26	GERP -3.5
Overall
CADD	0.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.54e-05% European (non-Finnish) · 1/1,171,470 alleles

Overall 6.3e-05% 1/1,587,812 alleles · very rare exomes 1/1,435,572 · genomes 0/152,240 · joint denominator

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.Ala737=
Coding: c.2211C>T
MANE Select: NM_020831
dbSNP: rs1281698349
Type: single nucleotide variant
Location: chr22:40418527 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 737: 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.Ala737Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
MRTFA p.Ala737Val 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-ala737 (accessed [today's date]).

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