Is MYRF p.Arg986Ter (c.2956C>T) pathogenic?

MYRF p.Arg986Ter (c.2956C>T) is classified Pathogenic in MYRF (ClinVar, Single submitter, 1 submitter). Absent from gnomAD v4.1; Associated with MYRF-related disorder.

What condition is associated with MYRF p.Arg986Ter (c.2956C>T)?

MYRF p.Arg986Ter (c.2956C>T) is associated with MYRF-related disorder (ClinVar).

How common is MYRF p.Arg986Ter (c.2956C>T) in the general population?

MYRF p.Arg986Ter (c.2956C>T) is absent from gnomAD v4.1 (gnomAD).

MYRF p.Arg986Ter

c.2956C>T · rs2541005761 · VCV2584483

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MYRF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 22 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.75, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYRF
Protein: p.Arg986Ter
Coding: c.2956C>T
MANE Select: NM_001127392
dbSNP: rs2541005761
Type: single nucleotide variant
Location: chr11:61781764 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 986: a UniProt-annotated variant site (in cugs; likely pathogenic); a UniProt-annotated variant site (in nno1; likely pathogenic)

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

Disease context

MYRF-related disorder

Similar variants

MYRF c.991+1G>A Likely pathogenic ★ same condition
MYRF p.Arg526His Likely pathogenic ★ same condition
MYRF p.Gln397Ter Likely pathogenic ★ same condition
MYRF p.Glu700Lys Likely pathogenic ★ same condition
MYRF p.Pro414Leu Likely pathogenic ★ same condition
MYRF p.Ser721Ter Likely pathogenic ★ same condition
MYRF p.Val379Met Likely pathogenic ★ same condition
MYRF p.Ala631Glu Uncertain significance ★ ⚠ 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-arg986ter (accessed [today's date]).

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