Is RELT p.Pro390Ser (c.1168C>T) pathogenic?

RELT p.Pro390Ser (c.1168C>T) is classified Uncertain significance in RELT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-31). AlphaMissense: likely benign (0.0622); Ultra-rare (popmax 0.0217%, amr); Associated with Inborn genetic diseases.

What condition is associated with RELT p.Pro390Ser (c.1168C>T)?

RELT p.Pro390Ser (c.1168C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RELT p.Pro390Ser (c.1168C>T) in the general population?

RELT p.Pro390Ser (c.1168C>T) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

What do computational predictors say about RELT p.Pro390Ser (c.1168C>T)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

RELT p.Pro390Ser

c.1168C>T · VCV3788192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.25	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 -0.95	GERP -4.1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	0.039	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 0.0217% Admixed American · 13/60,032 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00124% 20/1,613,346 alleles · ultra-rare exomes 20/1,461,022 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,618
South Asian	0.0022%	45,544
African / African-American	0.00133%	75,054
European (non-Finnish)	0.000339%	294,997

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.Pro390Ser
Coding: c.1168C>T
MANE Select: NM_152222
Type: single nucleotide variant
Location: chr11:73395208 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.38
Residue 390: the 'disordered' region

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.Pro390Ala Likely benign ★ same residue
RELT p.Pro390Thr Likely benign ★ 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

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-pro390ser (accessed [today's date]).

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