Is MRTFA p.Ala702= (c.2106G>A) pathogenic?

MRTFA p.Ala702= (c.2106G>A) is classified Benign/Likely benign in MRTFA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 35.9%, sas) — too common for a highly-penetrant pathogenic allele.

MRTFA p.Ala702=

Q: How common is MRTFA p.Ala702= (c.2106G>A) in the general population?

MRTFA p.Ala702= (c.2106G>A) is common (popmax 35.9%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2106G>A · rs4821944 · VCV1165223

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 35.9%, sas) — too common for a highly-penetrant pathogenic allele

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 -14	GERP -4.8
Overall
CADD	0.048	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 35.9% South Asian · 27,523/76,754 alleles

Filtering AF 35.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.4%

Overall 29.3% 446,995/1,526,442 alleles · common exomes 410,540/1,375,042 · genomes 36,455/151,400 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	35.9%	3
European (non-Finnish)	31.7%	3
Remaining individualsnot grpmax-eligible	27.8%	4
Amishnot grpmax-eligible	27.6%	4
Ashkenazi Jewishnot grpmax-eligible	26%	4
Middle Eastern	24.9%	4
Finnishnot grpmax-eligible	24.8%	4
Admixed American	16%	6
African / African-American	15.9%	6
East Asian	1.13%	88

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.Ala702=
Coding: c.2106G>A
MANE Select: NM_020831
dbSNP: rs4821944
Type: single nucleotide variant
Location: chr22:40418632 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 702: the 'disordered' region

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

Similar variants

MRTFA p.Ala702Val 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
MRTFA p.Ala537Val 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-ala702 (accessed [today's date]).

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