Is MRTFA p.Ala702Val (c.2105C>T) pathogenic?

MRTFA p.Ala702Val (c.2105C>T) is classified Uncertain significance in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.0762); Very rare (popmax 0.00226%, eas).

How common is MRTFA p.Ala702Val (c.2105C>T) in the general population?

MRTFA p.Ala702Val (c.2105C>T) is very rare (popmax 0.00226%, eas) (gnomAD).

What do computational predictors say about MRTFA p.Ala702Val (c.2105C>T)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

MRTFA p.Ala702Val

c.2105C>T · VCV3296156

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00226%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.082	GERP -3.6
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	8.585	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A602V vs ClinVar A702V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00226% East Asian · 1/44,182 alleles

Overall 0.000196% 3/1,527,376 alleles · very rare exomes 3/1,375,510 · genomes 0/151,866 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00226%	44,182
Remaining individualsnot grpmax-eligible	0.0017%	58,786
European (non-Finnish)	8.73e-05%	1,144,868

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.Ala702Val
Coding: c.2105C>T
MANE Select: NM_020831
Type: single nucleotide variant
Location: chr22:40418633 (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.Ala702= Benign/Likely benign ★★ 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-ala702val (accessed [today's date]).

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