Is MYRF p.Pro320Leu (c.959C>T) pathogenic?

MYRF p.Pro320Leu (c.959C>T) is classified Likely benign in MYRF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-25). AlphaMissense: ambiguous (0.3591); Very rare (popmax 0.00329%, sas).

How common is MYRF p.Pro320Leu (c.959C>T) in the general population?

MYRF p.Pro320Leu (c.959C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about MYRF p.Pro320Leu (c.959C>T)?

AlphaMissense predicts ambiguous (score 0.3591) — an in-silico prediction, not a clinical call.

MYRF p.Pro320Leu

c.959C>T · VCV4911829

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3591 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3591	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.71	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 2,379 bp · p 0.0002 · regional, not allelic
Overall
CADD	23.4	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 0.00329% South Asian · 3/91,052 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000606%

Overall 0.0013% 21/1,612,540 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,351
African / African-American	0.00267%	37,457
Remaining individualsnot grpmax-eligible	0.0016%	62,414
European (non-Finnish)	0.00127%	78,611

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.Pro320Leu
Coding: c.959C>T
MANE Select: NM_001127392
Type: single nucleotide variant
Location: chr11:61771718 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 320: the 'disordered' region; a DNA-binding region

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

Similar variants

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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-pro320leu (accessed [today's date]).

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