Is MYRF p.Pro188Ser (c.562C>T) pathogenic?

MYRF p.Pro188Ser (c.562C>T) is classified Uncertain significance in MYRF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.1072); Ultra-rare (popmax 0.0182%, amr); Associated with Inborn genetic diseases.

What condition is associated with MYRF p.Pro188Ser (c.562C>T)?

MYRF p.Pro188Ser (c.562C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MYRF p.Pro188Ser (c.562C>T) in the general population?

MYRF p.Pro188Ser (c.562C>T) is ultra-rare (popmax 0.0182%, amr) (gnomAD).

What do computational predictors say about MYRF p.Pro188Ser (c.562C>T)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

MYRF p.Pro188Ser

c.562C>T · VCV3298166

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -8.68	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 4.8	GERP 0.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.074 · regional, not allelic
Overall
CADD	24.4	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 0.0182% Admixed American · 9/49,404 alleles

Filtering AF 0.00944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00707%

Overall 0.00188% 21/1,115,382 alleles · ultra-rare exomes 12/964,976 · genomes 9/150,406 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0182%	5,489
African / African-American	0.00309%	32,342
Remaining individualsnot grpmax-eligible	0.00224%	44,728
European (non-Finnish)	0.00118%	84,996

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.Pro188Ser
Coding: c.562C>T
MANE Select: NM_001127392
Type: single nucleotide variant
Location: chr11:61770347 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 188: 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-pro188ser (accessed [today's date]).

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