Is MYRF p.Ser234Phe (c.701C>T) pathogenic?

MYRF p.Ser234Phe (c.701C>T) is classified Benign in MYRF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-09). AlphaMissense: likely benign (0.3294); Rare (popmax 0.469%, sas); Associated with MYRF-related disorder.

What condition is associated with MYRF p.Ser234Phe (c.701C>T)?

MYRF p.Ser234Phe (c.701C>T) is associated with MYRF-related disorder (ClinVar).

How common is MYRF p.Ser234Phe (c.701C>T) in the general population?

MYRF p.Ser234Phe (c.701C>T) is rare (popmax 0.469%, sas) (gnomAD).

What do computational predictors say about MYRF p.Ser234Phe (c.701C>T)?

AlphaMissense predicts likely benign (score 0.3294) — an in-silico prediction, not a clinical call.

MYRF p.Ser234Phe

c.701C>T · rs139124174 · VCV3050477

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3294 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.469%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MYRF-related disorder

Computational evidence

Protein change
AlphaMissense	0.3294	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -9.65	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 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 19 kb · p 0.074 · regional, not allelic
Overall
CADD	26.4	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 0.469% South Asian · 399/85,076 alleles

Filtering AF 0.431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.416%

Overall 0.0998% 1,563/1,565,352 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.02%	98
South Asiangrpmax	0.469%	213
Middle Eastern	0.0833%	1,201
Remaining individualsnot grpmax-eligible	0.0528%	1,894
European (non-Finnish)	0.0444%	2,251
African / African-American	0.00541%	18,481
Admixed American	0.00188%	53,280

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser234Phe
Coding: c.701C>T
MANE Select: NM_001127392
dbSNP: rs139124174
Type: single nucleotide variant
Location: chr11:61770486 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB

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-ser234phe (accessed [today's date]).

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