Is MRTFA p.Leu897Phe (c.2689C>T) pathogenic?

MRTFA p.Leu897Phe (c.2689C>T) is classified Uncertain significance in MRTFA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). AlphaMissense: likely benign (0.079); No allele count reported in gnomAD v4.1 (AN 1,527,106).

How common is MRTFA p.Leu897Phe (c.2689C>T) in the general population?

MRTFA p.Leu897Phe (c.2689C>T) is no allele count reported in gnomAD v4.1 (AN 1,527,106) (gnomAD).

What do computational predictors say about MRTFA p.Leu897Phe (c.2689C>T)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

MRTFA p.Leu897Phe

c.2689C>T · rs1309351773 · VCV2995232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,527,106)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -8.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	23.4	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 L797F vs ClinVar L897F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,527,106). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MRTFA
Protein: p.Leu897Phe
Coding: c.2689C>T
MANE Select: NM_020831
dbSNP: rs1309351773
Type: single nucleotide variant
Location: chr22:40411797 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 797 UniProt numbering: the 'disordered' region; 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

Similar variants

MRTFA p.Leu897= 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-leu897phe (accessed [today's date]).

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