Is MRTFA p.Pro734Ser (c.2200C>T) pathogenic?

MRTFA p.Pro734Ser (c.2200C>T) is classified Benign in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0776); Low-frequency (popmax 2.31%, afr).

How common is MRTFA p.Pro734Ser (c.2200C>T) in the general population?

MRTFA p.Pro734Ser (c.2200C>T) is low-frequency (popmax 2.31%, afr) (gnomAD).

What do computational predictors say about MRTFA p.Pro734Ser (c.2200C>T)?

AlphaMissense predicts likely benign (score 0.0776) — an in-silico prediction, not a clinical call.

MRTFA p.Pro734Ser

c.2200C>T · rs115175354 · VCV717869

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0776 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.31%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0776	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -8.31	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 1.9	GERP -1.1, phastCons 0.05
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	6.015	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P634S vs ClinVar P734S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.31% African / African-American · 1,705/73,748 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.18%

Overall 0.128% 2,023/1,584,692 alleles · low-frequency exomes 1,006/1,432,436 · genomes 1,017/152,256 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.31%	43
Remaining individualsnot grpmax-eligible	0.188%	531
Admixed American	0.187%	536
Middle Eastern	0.153%	656
European (non-Finnish)	0.00812%	12,310
South Asian	0.0023%	43,415

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.Pro734Ser
Coding: c.2200C>T
MANE Select: NM_020831
dbSNP: rs115175354
Type: single nucleotide variant
Location: chr22:40418538 (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.Pro734= Likely benign ★★ same residue
MRTFA p.Pro734Ala Uncertain significance ★ ⚠ same residue
MRTFA p.Pro734Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro734ser (accessed [today's date]).

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