Is MYRF p.Ser264fs (c.789del) pathogenic?

MYRF p.Ser264fs (c.789del) is classified Conflicting classifications of pathogenicity in MYRF (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-09-16). Absent from gnomAD v4.1; Associated with cardiac-urogenital syndrome.

What condition is associated with MYRF p.Ser264fs (c.789del)?

MYRF p.Ser264fs (c.789del) is associated with cardiac-urogenital syndrome (ClinVar).

How common is MYRF p.Ser264fs (c.789del) in the general population?

MYRF p.Ser264fs (c.789del) is absent from gnomAD v4.1 (gnomAD).

How is Cardiac-urogenital syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

MYRF p.Ser264fs

c.789del · rs769274302 · VCV1687467

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,020)

Conditions

cardiac-urogenital syndrome

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 6 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,020). 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: MYRF
Protein: p.Ser264fs
Coding: c.789del
MANE Select: NM_001127392
dbSNP: rs769274302
Type: Deletion
Location: chr11:61771541 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 264: a DNA-binding region

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

Disease context

cardiac-urogenital syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cardiac-urogenital syndrome (Orphanet):

Inheritance: Autosomal dominant

Similar variants

MYRF p.Asp568fs Likely pathogenic ★★ same condition
MYRF c.135-119_1062del Pathogenic ★ same condition
MYRF c.859_1591-84del Likely pathogenic ★ same condition
MYRF p.Gln1031fs Pathogenic ★ same condition
MYRF p.His215fs Likely pathogenic ★ same condition
MYRF p.Ser350fs Likely pathogenic ★ same condition
MYRF p.Val1070fs Likely pathogenic ★ same condition
MYRF p.Ser264Arg Uncertain significance ★ ⚠ same residue

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-ser264fs (accessed [today's date]).

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