Is MYRF p.Ser803Phe (c.2408C>T) pathogenic?

MYRF p.Ser803Phe (c.2408C>T) is classified Likely benign in MYRF (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-24). AlphaMissense: likely benign (0.1698); Rare (popmax 0.103%, afr).

How common is MYRF p.Ser803Phe (c.2408C>T) in the general population?

MYRF p.Ser803Phe (c.2408C>T) is rare (popmax 0.103%, afr) (gnomAD).

What do computational predictors say about MYRF p.Ser803Phe (c.2408C>T)?

AlphaMissense predicts likely benign (score 0.1698) — an in-silico prediction, not a clinical call.

MYRF p.Ser803Phe

c.2408C>T · rs193033927 · VCV3031629

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1698 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1698	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -8.00	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 1.7, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 4,034 bp · p 0.0022 · regional, not allelic
Overall
CADD	23.6	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 0.103% African / African-American · 75/73,162 alleles

Filtering AF 0.0838% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0769%

Overall 0.0051% 79/1,550,042 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	975
Remaining individualsnot grpmax-eligible	0.00332%	30,101
Admixed American	0.00196%	51,006
European (non-Finnish)	8.72e-05%	1,147,048

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.Ser803Phe
Coding: c.2408C>T
MANE Select: NM_001127392
dbSNP: rs193033927
Type: single nucleotide variant
Location: chr11:61780714 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 803: a UniProt-annotated variant site (in cugs; likely pathogenic)

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

Similar variants

MYRF p.Gln150Ter Pathogenic/Likely pathogenic ★★ same type
MYRF p.Trp939Ter Pathogenic ★★ same type
MYRF p.Ala1001Ser Uncertain significance ★★ ⚠ same type
MYRF p.Arg174Cys Uncertain significance ★★ ⚠ same type
MYRF p.Arg733Gln Uncertain significance ★★ ⚠ same type
MYRF p.Asn267Ser Uncertain significance ★★ ⚠ same type
MYRF p.Glu421Lys Uncertain significance ★★ ⚠ same type
MYRF p.Pro743Ser Uncertain significance ★★ ⚠ same type

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-ser803phe (accessed [today's date]).

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