Is QRFPR p.Leu186Ile (c.556C>A) pathogenic?

QRFPR p.Leu186Ile (c.556C>A) is classified Uncertain significance in QRFPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.1439); No allele count reported in gnomAD v4.1 (AN 1,612,186).

How common is QRFPR p.Leu186Ile (c.556C>A) in the general population?

QRFPR p.Leu186Ile (c.556C>A) is no allele count reported in gnomAD v4.1 (AN 1,612,186) (gnomAD).

What do computational predictors say about QRFPR p.Leu186Ile (c.556C>A)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

QRFPR p.Leu186Ile

c.556C>A · VCV3785829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,186)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -7.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 51 kb · p 0.68 · regional, not allelic
Overall
CADD	26.3	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

No allele count reported in gnomAD v4.1 (AN 1,612,186). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: QRFPR
Protein: p.Leu186Ile
Coding: c.556C>A
MANE Select: NM_198179
Type: single nucleotide variant
Location: chr4:121336812 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.74 · 2 PDB
Residue 186: a β-strand

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-leu186ile (accessed [today's date]).

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