Is QRFPR p.Met136Val (c.406A>G) pathogenic?

QRFPR p.Met136Val (c.406A>G) is classified Uncertain significance in QRFPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: likely benign (0.277); Very rare (popmax 0.00133%, afr).

How common is QRFPR p.Met136Val (c.406A>G) in the general population?

QRFPR p.Met136Val (c.406A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about QRFPR p.Met136Val (c.406A>G)?

AlphaMissense predicts likely benign (score 0.277) — an in-silico prediction, not a clinical call.

QRFPR p.Met136Val

c.406A>G · VCV3428862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.277 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.277	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.79, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 51 kb · p 0.68 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,050 alleles

Overall 0.000124% 2/1,614,086 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,050
South Asian	0.0011%	91,076

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: QRFPR
Protein: p.Met136Val
Coding: c.406A>G
MANE Select: NM_198179
Type: single nucleotide variant
Location: chr4:121340545 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.74 · 2 PDB
Residue 136: an α-helix

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

Similar variants

QRFPR p.Ile296Thr Uncertain significance ★★ ⚠ same type
QRFPR p.Ala128Thr Uncertain significance ★ ⚠ same type
QRFPR p.Ala315Val Uncertain significance ★ ⚠ same type
QRFPR p.Arg13Trp Uncertain significance ★ ⚠ same type
QRFPR p.Arg160Gln Uncertain significance ★ ⚠ same type
QRFPR p.Arg161Thr Uncertain significance ★ ⚠ same type
QRFPR p.Arg16Pro Uncertain significance ★ same type
QRFPR p.Arg22Gln 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/qrfpr-p-met136val (accessed [today's date]).

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