Is RELT p.Arg129Pro (c.386G>C) pathogenic?

RELT p.Arg129Pro (c.386G>C) is classified Uncertain significance in RELT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely benign (0.1351); Very rare (popmax 0.0033%, sas); Associated with Inborn genetic diseases.

What condition is associated with RELT p.Arg129Pro (c.386G>C)?

RELT p.Arg129Pro (c.386G>C) is associated with Inborn genetic diseases (ClinVar).

How common is RELT p.Arg129Pro (c.386G>C) in the general population?

RELT p.Arg129Pro (c.386G>C) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about RELT p.Arg129Pro (c.386G>C)?

AlphaMissense predicts likely benign (score 0.1351) — an in-silico prediction, not a clinical call.

RELT p.Arg129Pro

c.386G>C · VCV3432058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1351 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1351	likely benign
REVEL	0.407	indeterminate
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/90,872 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000186% 3/1,611,384 alleles · very rare exomes 2/1,459,180 · genomes 1/152,204 · joint denominator

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.Arg129Pro
Coding: c.386G>C
MANE Select: NM_152222
Type: single nucleotide variant
Location: chr11:73392229 (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.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
RELT p.Arg126Trp 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-arg129pro (accessed [today's date]).

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