Is REL p.Arg278= (c.834A>G) pathogenic?

REL p.Arg278= (c.834A>G) is classified Benign/Likely benign in REL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-12). Rare (popmax 0.591%, sas).

How common is REL p.Arg278= (c.834A>G) in the general population?

REL p.Arg278= (c.834A>G) is rare (popmax 0.591%, sas) (gnomAD).

REL p.Arg278=

c.834A>G · rs562343804 · VCV2144759

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.591%, 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 1.7	GERP -3.7, phastCons 1
Overall
CADD	12.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.591% South Asian · 538/91,052 alleles

Filtering AF 0.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.533%

Overall 0.0346% 558/1,612,988 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.591%	169
Middle Eastern	0.0495%	2,020
Remaining individualsnot grpmax-eligible	0.0272%	3,676

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.Arg278=
Coding: c.834A>G
MANE Select: NM_001291746
dbSNP: rs562343804
Type: single nucleotide variant
Location: chr2:60918587 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.46
Residue 278: the rhd domain

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

Similar variants

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
REL p.Ser556Gly Uncertain significance ★★ ⚠ same type
REL p.Ser563Asn 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-arg278 (accessed [today's date]).

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