Is REL p.Pro361Arg (c.1082C>G) pathogenic?

REL p.Pro361Arg (c.1082C>G) is classified Benign/Likely benign in REL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-12). AlphaMissense: likely benign (0.1191); Low-frequency (popmax 1.93%, afr).

How common is REL p.Pro361Arg (c.1082C>G) in the general population?

REL p.Pro361Arg (c.1082C>G) is low-frequency (popmax 1.93%, afr) (gnomAD).

What do computational predictors say about REL p.Pro361Arg (c.1082C>G)?

AlphaMissense predicts likely benign (score 0.1191) — an in-silico prediction, not a clinical call.

REL p.Pro361Arg

c.1082C>G · rs34661029 · VCV790504

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1191 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.93%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1191	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.98	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 4.9	GERP 0.53, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 1,945 bp · p 0.96 · regional, not allelic
Overall
CADD	16.93	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P393R vs ClinVar P361R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.93% African / African-American · 1,448/75,014 alleles

Filtering AF 1.85% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.81%

Overall 0.102% 1,647/1,614,094 alleles · low-frequency exomes 788/1,461,866 · genomes 859/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.93%	52
Admixed American	0.127%	789
Remaining individualsnot grpmax-eligible	0.118%	845
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.00364%	27,442
South Asian	0.0022%	45,539

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: REL
Protein: p.Pro361Arg
Coding: c.1082C>G
MANE Select: NM_001291746
dbSNP: rs34661029
Type: single nucleotide variant
Location: chr2:60921853 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.46

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

Similar variants

REL p.Pro361Thr Uncertain significance ★ ⚠ same residue
REL p.Pro361= Likely benign ★ same residue
REL p.Asp224Asn Uncertain significance ★★ ⚠ same type
REL p.Gln503His Uncertain significance ★★ ⚠ same type
REL p.Leu298Val Uncertain significance ★★ ⚠ same type
REL p.Met372Lys Uncertain significance ★★ ⚠ same type
REL p.Met372Val Uncertain significance ★★ ⚠ same type
REL p.Phe559Leu 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/rel-p-pro361arg (accessed [today's date]).

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