Is MYRF p.Pro93Ser (c.277C>T) pathogenic?

MYRF p.Pro93Ser (c.277C>T) is classified Uncertain significance in MYRF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-11). AlphaMissense: likely benign (0.0747); Absent from gnomAD v4.1.

How common is MYRF p.Pro93Ser (c.277C>T) in the general population?

MYRF p.Pro93Ser (c.277C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYRF p.Pro93Ser (c.277C>T)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

MYRF p.Pro93Ser

c.277C>T · rs2540856342 · VCV2434003

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -7.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.074 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro93Ser
Coding: c.277C>T
MANE Select: NM_001127392
dbSNP: rs2540856342
Type: single nucleotide variant
Location: chr11:61766100 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 93: the 'disordered' region

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

Similar variants

MYRF p.Pro93Leu Uncertain significance ★ ⚠ same residue
MYRF p.Pro93fs Pathogenic ★ same residue
MYRF p.Gln150Ter Pathogenic/Likely pathogenic ★★ same type
MYRF p.Trp939Ter Pathogenic ★★ same type
MYRF p.Ala1001Ser Uncertain significance ★★ ⚠ same type
MYRF p.Arg174Cys Uncertain significance ★★ ⚠ same type
MYRF p.Arg733Gln Uncertain significance ★★ ⚠ same type
MYRF p.Asn267Ser 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/myrf-p-pro93ser (accessed [today's date]).

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