Is MYRF p.Phe387Ser (c.1160T>C) pathogenic?

MYRF p.Phe387Ser (c.1160T>C) is classified Likely pathogenic in MYRF (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with urogenital tract malformation.

What condition is associated with MYRF p.Phe387Ser (c.1160T>C)?

MYRF p.Phe387Ser (c.1160T>C) is associated with urogenital tract malformation (ClinVar).

How common is MYRF p.Phe387Ser (c.1160T>C) in the general population?

MYRF p.Phe387Ser (c.1160T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYRF p.Phe387Ser (c.1160T>C)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

MYRF p.Phe387Ser

c.1160T>C · rs2066302424 · VCV996606

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

urogenital tract malformation

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic ✓ concordant with ClinVar · top 3% in MYRF
REVEL	0.67	pathogenic-leaning
SaProt	LLR -11.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 2,379 bp · p 0.0002 · regional, not allelic
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Phe387Ser
Coding: c.1160T>C
MANE Select: NM_001127392
dbSNP: rs2066302424
Type: single nucleotide variant
Location: chr11:61774011 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 387: a β-strand; a DNA-binding region

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

Disease context

urogenital tract malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYRF p.Gln596Ter Likely pathogenic ★ same condition
MYRF p.Leu479Val Pathogenic ★ same condition
MYRF p.Arg695His Uncertain significance ★ ⚠ same condition
MYRF p.Val679Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
MYRF c.1904-1G>A Likely pathogenic same condition
MYRF p.Gln403His Likely pathogenic same condition
MYRF p.Gly435Arg Pathogenic/Likely pathogenic same condition
MYRF p.Gly81fs 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-phe387ser (accessed [today's date]).

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