Is RELT p.Arg8Trp (c.22C>T) pathogenic?

RELT p.Arg8Trp (c.22C>T) is classified Likely benign in RELT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-05). AlphaMissense: likely benign (0.0509); Ultra-rare (popmax 0.0355%, mid); Associated with Inborn genetic diseases.

What condition is associated with RELT p.Arg8Trp (c.22C>T)?

RELT p.Arg8Trp (c.22C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RELT p.Arg8Trp (c.22C>T) in the general population?

RELT p.Arg8Trp (c.22C>T) is ultra-rare (popmax 0.0355%, mid) (gnomAD).

What do computational predictors say about RELT p.Arg8Trp (c.22C>T)?

AlphaMissense predicts likely benign (score 0.0509) — an in-silico prediction, not a clinical call.

RELT p.Arg8Trp

c.22C>T · VCV3313597

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0355%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0509	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -6.04	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 1.1	GERP -3.4, phastCons 0.98
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	8.908	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0355% Middle Eastern · 2/5,636 alleles

Filtering AF 0.00622% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00257%

Overall 0.0031% 48/1,550,842 alleles · ultra-rare exomes 39/1,398,652 · genomes 9/152,190 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0355%	2,818
Finnishnot grpmax-eligible	0.0325%	3,073
African / African-American	0.00549%	18,232
European (non-Finnish)	0.002%	49,904

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: RELT
Protein: p.Arg8Trp
Coding: c.22C>T
MANE Select: NM_152222
Type: single nucleotide variant
Location: chr11:73389158 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.38

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RELT p.Arg8Gln Uncertain significance ★ ⚠ same residue
RELT p.Ala136Val Uncertain significance ★ ⚠ same condition
RELT p.Ala164Thr Uncertain significance ★ ⚠ same condition
RELT p.Ala164Val Uncertain significance ★ ⚠ same condition
RELT p.Ala239Val Uncertain significance ★ ⚠ same condition
RELT p.Ala267Val Uncertain significance ★ ⚠ same condition
RELT p.Ala353Thr Uncertain significance ★ ⚠ same condition
RELT p.Ala410Ser Uncertain significance ★ ⚠ 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/relt-p-arg8trp (accessed [today's date]).

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