Is MYRF p.Arg606Ser (c.1818G>C) pathogenic?

MYRF p.Arg606Ser (c.1818G>C) is classified Uncertain significance in MYRF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: likely pathogenic (0.9559); Very rare (popmax 0.000174%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYRF p.Arg606Ser (c.1818G>C)?

MYRF p.Arg606Ser (c.1818G>C) is associated with Inborn genetic diseases (ClinVar).

How common is MYRF p.Arg606Ser (c.1818G>C) in the general population?

MYRF p.Arg606Ser (c.1818G>C) is very rare (popmax 0.000174%, nfe) (gnomAD).

What do computational predictors say about MYRF p.Arg606Ser (c.1818G>C)?

AlphaMissense predicts likely pathogenic (score 0.9559) — an in-silico prediction, not a clinical call.

MYRF p.Arg606Ser

c.1818G>C · VCV4625676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9559 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9559	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -11.87	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.53, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 2,098 bp · p 2.6e-09 · regional, not allelic
Overall
CADD	24.9	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

Grpmax group 0.000174% European (non-Finnish) · 2/1,147,076 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000143% 2/1,399,602 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYRF
Protein: p.Arg606Ser
Coding: c.1818G>C
MANE Select: NM_001127392
Type: single nucleotide variant
Location: chr11:61777760 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 606: a UniProt-annotated variant site (in cugs; likely pathogenic); the peptidase s74 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYRF p.Arg606Thr Uncertain significance ★ ⚠ same residue
MYRF p.Ala1001Ser Uncertain significance ★★ ⚠ same condition
MYRF p.Arg174Cys Uncertain significance ★★ ⚠ same condition
MYRF p.Arg733Gln Uncertain significance ★★ ⚠ same condition
MYRF p.Asn267Ser Uncertain significance ★★ ⚠ same condition
MYRF p.Pro743Ser Uncertain significance ★★ ⚠ same condition
MYRF p.Thr1102Ile Uncertain significance ★★ ⚠ same condition
MYRF p.Gly96Ser Likely benign ★★ 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-arg606ser (accessed [today's date]).

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