Is MYRF p.Ser975fs (c.2925_2944del) pathogenic?

MYRF p.Ser975fs (c.29252944del) is classified Likely pathogenic in MYRF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-12). Associated with MYRF-related disorder.

What condition is associated with MYRF p.Ser975fs (c.2925_2944del)?

MYRF p.Ser975fs (c.2925_2944del) is associated with MYRF-related disorder (ClinVar).

MYRF p.Ser975fs

c.2925_2944del · VCV4911884

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

MYRF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 22 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP -0.27, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MYRF
Protein: p.Ser975fs
Coding: c.2925_2944del
MANE Select: NM_001127392
Type: Deletion
Location: chr11:61781732 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 975: a UniProt-annotated variant site (in cugs; likely pathogenic)

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

Disease context

MYRF-related disorder

Similar variants

MYRF p.Thr472fs Likely pathogenic ★ same condition
MYRF p.Arg478fs Likely pathogenic same condition
MYRF p.Leu479fs Likely pathogenic same condition
MYRF c.991+1G>A Likely pathogenic ★ same condition
MYRF p.Arg526His Likely pathogenic ★ same condition
MYRF p.Arg616fs Likely pathogenic ★ same condition
MYRF p.Arg986Ter Pathogenic ★ same condition
MYRF p.Gln397Ter Likely pathogenic ★ same condition

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/myrf-p-ser975fs (accessed [today's date]).

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