Is MRTFA p.Gly548= (c.1644C>T) pathogenic?

MRTFA p.Gly548= (c.1644C>T) is classified Likely benign in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-11). Ultra-rare (popmax 0.0159%, eas).

How common is MRTFA p.Gly548= (c.1644C>T) in the general population?

MRTFA p.Gly548= (c.1644C>T) is ultra-rare (popmax 0.0159%, eas) (gnomAD).

MRTFA p.Gly548=

c.1644C>T · rs979882578 · VCV1121247

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0159%, eas)

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	GERP -0.61, phastCons 1
Overall
CADD	3.613	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0159% East Asian · 7/43,948 alleles

Filtering AF 0.00739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00523%

Overall 0.0025% 40/1,598,228 alleles · ultra-rare exomes 38/1,446,086 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0159%	6,278
South Asian	0.00448%	22,327
African / African-American	0.00403%	24,791
European (non-Finnish)	0.00213%	46,918
Finnishnot grpmax-eligible	0.00163%	61,414

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.Gly548=
Coding: c.1644C>T
MANE Select: NM_020831
dbSNP: rs979882578
Type: single nucleotide variant
Location: chr22:40419094 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB

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

Similar variants

MRTFA p.Gly548Val Uncertain significance ★★ ⚠ same residue
MRTFA p.Gly548Asp Uncertain significance ★ ⚠ same residue
MRTFA p.Gly548Ser 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

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-gly548 (accessed [today's date]).

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