Is RELT p.Ala239Val (c.716C>T) pathogenic?

RELT p.Ala239Val (c.716C>T) is classified Uncertain significance in RELT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1273); Ultra-rare (popmax 0.0102%, amr); Associated with Inborn genetic diseases.

What condition is associated with RELT p.Ala239Val (c.716C>T)?

RELT p.Ala239Val (c.716C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RELT p.Ala239Val (c.716C>T) in the general population?

RELT p.Ala239Val (c.716C>T) is ultra-rare (popmax 0.0102%, amr) (gnomAD).

What do computational predictors say about RELT p.Ala239Val (c.716C>T)?

AlphaMissense predicts likely benign (score 0.1273) — an in-silico prediction, not a clinical call.

RELT p.Ala239Val

c.716C>T · rs528226560 · VCV2388334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1273 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1273	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -8.64	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	GERP -0.008, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	25.1	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 0.0102% Admixed American · 6/58,566 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00301%

Overall 0.00336% 54/1,605,732 alleles · ultra-rare exomes 49/1,453,612 · genomes 5/152,120 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0102%	9,761
European (non-Finnish)	0.00374%	26,743
East Asian	0.00224%	44,650
Remaining individualsnot grpmax-eligible	0.00161%	62,128
African / African-American	0.00134%	74,752
South Asian	0.00111%	90,052

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.Ala239Val
Coding: c.716C>T
MANE Select: NM_152222
dbSNP: rs528226560
Type: single nucleotide variant
Location: chr11:73394245 (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.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
RELT p.Arg129Pro 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-ala239val (accessed [today's date]).

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