Is QRFPR p.Gln211Glu (c.631C>G) pathogenic?

QRFPR p.Gln211Glu (c.631C>G) is classified Uncertain significance in QRFPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1181); Rare (popmax 0.151%, mid).

How common is QRFPR p.Gln211Glu (c.631C>G) in the general population?

QRFPR p.Gln211Glu (c.631C>G) is rare (popmax 0.151%, mid) (gnomAD).

What do computational predictors say about QRFPR p.Gln211Glu (c.631C>G)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

QRFPR p.Gln211Glu

c.631C>G · rs139685422 · VCV2378069

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.22	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 51 kb · p 0.68 · regional, not allelic
Overall
CADD	23.5	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 0.151% Middle Eastern · 9/5,978 alleles

Filtering AF 0.0785% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0586%

Overall 0.0312% 493/1,581,994 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.151%	664
Ashkenazi Jewishnot grpmax-eligible	0.09%	1,111
Admixed American	0.0546%	1,830
Remaining individualsnot grpmax-eligible	0.042%	2,383
European (non-Finnish)	0.0329%	3,035
Finnishnot grpmax-eligible	0.00958%	10,443
South Asian	0.00668%	14,968
African / African-American	0.00607%	16,472
East Asian	0.00228%	43,770

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.Gln211Glu
Coding: c.631C>G
MANE Select: NM_198179
dbSNP: rs139685422
Type: single nucleotide variant
Location: chr4:121332987 (GRCh38)
Gene constraint: LOEUF 1.532 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.74 · 2 PDB
Residue 211: 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-gln211glu (accessed [today's date]).

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