Is MYRF p.Ala805= (c.2415C>T) pathogenic?

MYRF p.Ala805= (c.2415C>T) is classified Likely benign in MYRF (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-21). Rare (popmax 0.491%, sas).

How common is MYRF p.Ala805= (c.2415C>T) in the general population?

MYRF p.Ala805= (c.2415C>T) is rare (popmax 0.491%, sas) (gnomAD).

MYRF p.Ala805=

c.2415C>T · rs142182853 · VCV3049508

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.491%, sas)

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 -1.6	GERP -2
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.491% South Asian · 413/84,068 alleles

Filtering AF 0.452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.437%

Overall 0.1% 1,552/1,549,876 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.981%	102
South Asiangrpmax	0.491%	204
Middle Eastern	0.0668%	1,497
Remaining individualsnot grpmax-eligible	0.0548%	1,824
European (non-Finnish)	0.046%	2,172
African / African-American	0.00547%	18,290
East Asian	0.00487%	20,528
Admixed American	0.00196%	51,000

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.Ala805=
Coding: c.2415C>T
MANE Select: NM_001127392
dbSNP: rs142182853
Type: single nucleotide variant
Location: chr11:61780721 (GRCh38)
Gene constraint: LOEUF 0.215 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.76 · 2 PDB
Residue 805: 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-ala805 (accessed [today's date]).

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