Is RIGI p.Phe579= (c.1737C>T) pathogenic?

RIGI p.Phe579= (c.1737C>T) is classified Benign/Likely benign in RIGI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.74%, afr); Associated with Singleton-Merten syndrome 2.

What condition is associated with RIGI p.Phe579= (c.1737C>T)?

RIGI p.Phe579= (c.1737C>T) is associated with Singleton-Merten syndrome 2 (ClinVar).

How common is RIGI p.Phe579= (c.1737C>T) in the general population?

RIGI p.Phe579= (c.1737C>T) is low-frequency (popmax 1.74%, afr) (gnomAD).

RIGI p.Phe579=

c.1737C>T · rs116612738 · VCV786134

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.74%, afr)

Conditions

Singleton-Merten syndrome 2

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 3	GERP -2.7, phastCons 1
Overall
CADD	9.669	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.74% African / African-American · 1,306/74,944 alleles

Filtering AF 1.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.63%

Overall 0.0962% 1,548/1,609,742 alleles · low-frequency exomes 812/1,457,562 · genomes 736/152,180 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.74%	57
Remaining individualsnot grpmax-eligible	0.144%	692
Admixed American	0.124%	810
Middle Eastern	0.0826%	1,210
European (non-Finnish)	0.00603%	16,576
East Asian	0.00223%	44,796
South Asian	0.0011%	90,568

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: RIGI
Protein: p.Phe579=
Coding: c.1737C>T
MANE Select: NM_014314
dbSNP: rs116612738
Type: single nucleotide variant
Location: chr9:32480256 (GRCh38)
Structure: AlphaFold pLDDT 85.40 · 44 PDB
Residue 579: an α-helix; the 'interaction with zc3hav1' region

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

Disease context

Singleton-Merten syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RIGI p.Arg866Ter Uncertain significance ★★ same condition
RIGI p.Leu100Val Uncertain significance ★★ ⚠ same condition
RIGI p.Ser411Leu Uncertain significance ★★ ⚠ same condition
RIGI p.Val293Leu Uncertain significance ★★ ⚠ same condition
RIGI c.2337+11G>A Benign/Likely benign ★★ same condition
RIGI p.Asn245Ser Benign/Likely benign ★★ same condition
RIGI p.Asn353= Benign/Likely benign ★★ same condition
RIGI p.Asp580Glu Benign/Likely benign ★★ same condition

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/rigi-p-phe579 (accessed [today's date]).

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