Is REL p.Ser579= (c.1737C>T) pathogenic?

REL p.Ser579= (c.1737C>T) is classified Likely benign in REL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-17). Very rare (popmax 0.00112%, sas).

How common is REL p.Ser579= (c.1737C>T) in the general population?

REL p.Ser579= (c.1737C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

REL p.Ser579=

c.1737C>T · rs548696092 · VCV1977223

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, 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 -0.97	GERP -3
Overall
CADD	0.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,520 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000312% 5/1,603,262 alleles · very rare exomes 4/1,451,072 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,520
European (non-Finnish)	0.00034%	293,695

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.Ser579=
Coding: c.1737C>T
MANE Select: NM_001291746
dbSNP: rs548696092
Type: single nucleotide variant
Location: chr2:60922508 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.46
Residue 579: the 'disordered' region

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-ser579 (accessed [today's date]).

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