Is MYRF p.Pro194Ser (c.580C>T) pathogenic?

MYRF p.Pro194Ser (c.580C>T) is classified Uncertain significance in MYRF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.0898); Very rare (popmax 0.00317%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MYRF p.Pro194Ser (c.580C>T)?

MYRF p.Pro194Ser (c.580C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYRF p.Pro194Ser (c.580C>T) in the general population?

MYRF p.Pro194Ser (c.580C>T) is very rare (popmax 0.00317%, nfe) (gnomAD).

What do computational predictors say about MYRF p.Pro194Ser (c.580C>T)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

MYRF p.Pro194Ser

c.580C>T · rs748967830 · VCV3169656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00317%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.074 · regional, not allelic
Overall
CADD	21.2	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

Grpmax group 0.00317% European (non-Finnish) · 36/1,134,552 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.00241% 37/1,533,380 alleles · very rare exomes 33/1,381,512 · genomes 4/151,868 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00317%	31,515
Remaining individualsnot grpmax-eligible	0.00168%	59,424

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.Pro194Ser
Coding: c.580C>T
MANE Select: NM_001127392
dbSNP: rs748967830
Type: single nucleotide variant
Location: chr11:61770365 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 194: the 'disordered' region

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.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
MYRF p.Gln403Ter 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-pro194ser (accessed [today's date]).

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