Is RELT p.Pro203Ser (c.607C>T) pathogenic?

RELT p.Pro203Ser (c.607C>T) is classified Uncertain significance in RELT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). AlphaMissense: likely benign (0.0752); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RELT p.Pro203Ser (c.607C>T)?

RELT p.Pro203Ser (c.607C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RELT p.Pro203Ser (c.607C>T) in the general population?

RELT p.Pro203Ser (c.607C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RELT p.Pro203Ser (c.607C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

RELT p.Pro203Ser

c.607C>T · rs2496009626 · VCV2478971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.80	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 -0.025	GERP -1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	11.15	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RELT
Protein: p.Pro203Ser
Coding: c.607C>T
MANE Select: NM_152222
dbSNP: rs2496009626
Type: single nucleotide variant
Location: chr11:73392450 (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-pro203ser (accessed [today's date]).

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