Is MRTFA p.Thr760= (c.2280C>T) pathogenic?

MRTFA p.Thr760= (c.2280C>T) is classified Conflicting classifications of pathogenicity in MRTFA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-06). Ultra-rare (popmax 0.0187%, sas); Associated with immunodeficiency 66.

What condition is associated with MRTFA p.Thr760= (c.2280C>T)?

MRTFA p.Thr760= (c.2280C>T) is associated with immunodeficiency 66 (ClinVar).

How common is MRTFA p.Thr760= (c.2280C>T) in the general population?

MRTFA p.Thr760= (c.2280C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

MRTFA p.Thr760=

c.2280C>T · rs774753571 · VCV1675102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Conditions

immunodeficiency 66

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 -3.4	GERP -4.6
Overall
CADD	0.862	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,092 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00341% 55/1,613,862 alleles · ultra-rare exomes 43/1,461,712 · genomes 12/152,150 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0187%	5,358
African / African-American	0.0107%	9,364
Remaining individualsnot grpmax-eligible	0.0096%	10,412
Admixed American	0.00834%	11,998
East Asian	0.00223%	44,872
European (non-Finnish)	0.00153%	65,551

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.Thr760=
Coding: c.2280C>T
MANE Select: NM_020831
dbSNP: rs774753571
Type: single nucleotide variant
Location: chr22:40418458 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 760: 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

Disease context

immunodeficiency 66 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MRTFA p.Ala636Val Uncertain significance ★★ ⚠ same condition
MRTFA p.Arg639His Uncertain significance ★★ ⚠ same condition
MRTFA p.Asp942Asn Uncertain significance ★★ ⚠ same condition
MRTFA p.Met976Ile Uncertain significance ★★ ⚠ same condition
MRTFA p.Ser435Leu Uncertain significance ★★ ⚠ same condition
MRTFA p.Val553Met Uncertain significance ★★ ⚠ same condition
MRTFA p.Val675Met Uncertain significance ★★ ⚠ same condition
MRTFA p.Leu749Ile Benign/Likely benign ★★ same condition

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-thr760 (accessed [today's date]).

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