Is MRTFA p.Ser315Phe (c.944C>T) pathogenic?

MRTFA p.Ser315Phe (c.944C>T) is classified Uncertain significance in MRTFA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1508); Very rare (popmax 0.00689%, afr).

How common is MRTFA p.Ser315Phe (c.944C>T) in the general population?

MRTFA p.Ser315Phe (c.944C>T) is very rare (popmax 0.00689%, afr) (gnomAD).

What do computational predictors say about MRTFA p.Ser315Phe (c.944C>T)?

AlphaMissense predicts likely benign (score 0.1508) — an in-silico prediction, not a clinical call.

MRTFA p.Ser315Phe

c.944C>T · rs148143612 · VCV1683127

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00689%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1508	likely benign
REVEL	0.376	indeterminate
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.5	GERP 0.38, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.043 · regional, not allelic
Overall
CADD	23.7	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 S215F vs ClinVar S315F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00689% African / African-American · 5/72,530 alleles

Filtering AF 0.00271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.000521% 8/1,534,294 alleles · very rare exomes 3/1,382,136 · genomes 5/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00689%	14,506
European (non-Finnish)	0.000263%	379,564

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.Ser315Phe
Coding: c.944C>T
MANE Select: NM_020831
dbSNP: rs148143612
Type: single nucleotide variant
Location: chr22:40421084 (GRCh38)
Gene constraint: LOEUF 0.389 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.59 · 2 PDB
Residue 215 UniProt numbering: the 'mediates interaction with scai and actb' region; the 'disordered' region

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

Similar variants

MRTFA p.Ser315Ala 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-ser315phe (accessed [today's date]).

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