Is MYRF p.Ala57= (c.171C>T) pathogenic?

MYRF p.Ala57= (c.171C>T) is classified Likely benign in MYRF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-25). Ultra-rare (popmax 0.0206%, eas); Associated with MYRF-related disorder.

What condition is associated with MYRF p.Ala57= (c.171C>T)?

MYRF p.Ala57= (c.171C>T) is associated with MYRF-related disorder (ClinVar).

How common is MYRF p.Ala57= (c.171C>T) in the general population?

MYRF p.Ala57= (c.171C>T) is ultra-rare (popmax 0.0206%, eas) (gnomAD).

MYRF p.Ala57=

c.171C>T · rs746693238 · VCV3047759

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0206%, eas)

Conditions

MYRF-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.7, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0206% East Asian · 9/43,724 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00797%

Overall 0.000573% 9/1,569,758 alleles · ultra-rare exomes 8/1,417,474 · genomes 1/152,284 · joint denominator

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.Ala57=
Coding: c.171C>T
MANE Select: NM_001127392
dbSNP: rs746693238
Type: single nucleotide variant
Location: chr11:61765994 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 57: the 'disordered' region

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

Disease context

MYRF-related disorder

Similar variants

MYRF c.991+1G>A Likely pathogenic ★ same condition
MYRF p.Arg526His Likely pathogenic ★ same condition
MYRF p.Arg986Ter Pathogenic ★ same condition
MYRF p.Gln397Ter Likely pathogenic ★ same condition
MYRF p.Glu700Lys Likely pathogenic ★ same condition
MYRF p.Pro414Leu Likely pathogenic ★ same condition
MYRF p.Ser721Ter Likely pathogenic ★ same condition
MYRF p.Val379Met 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-ala57 (accessed [today's date]).

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