Is RELT p.Val367Glu (c.1100T>A) pathogenic?

RELT p.Val367Glu (c.1100T>A) is classified Benign in RELT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-03). AlphaMissense: likely benign (0.2012); Low-frequency (popmax 3.18%, afr); Associated with RELT-related disorder.

What condition is associated with RELT p.Val367Glu (c.1100T>A)?

RELT p.Val367Glu (c.1100T>A) is associated with RELT-related disorder (ClinVar).

How common is RELT p.Val367Glu (c.1100T>A) in the general population?

RELT p.Val367Glu (c.1100T>A) is low-frequency (popmax 3.18%, afr) (gnomAD).

What do computational predictors say about RELT p.Val367Glu (c.1100T>A)?

AlphaMissense predicts likely benign (score 0.2012) — an in-silico prediction, not a clinical call.

RELT p.Val367Glu

c.1100T>A · rs141011672 · VCV3044723

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2012 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.18%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RELT-related disorder

Computational evidence

Protein change
AlphaMissense	0.2012	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -5.21	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 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	21.1	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 3.18% African / African-American · 2,388/74,980 alleles

Filtering AF 3.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.04%

Overall 0.175% 2,821/1,613,566 alleles · low-frequency exomes 1,464/1,461,372 · genomes 1,357/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.18%	31
Admixed American	0.267%	375
Remaining individualsnot grpmax-eligible	0.264%	379
Middle Eastern	0.181%	551
South Asian	0.00769%	13,012
European (non-Finnish)	0.00754%	13,258
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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.Val367Glu
Coding: c.1100T>A
MANE Select: NM_152222
dbSNP: rs141011672
Type: single nucleotide variant
Location: chr11:73395140 (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

RELT-related disorder

Similar variants

RELT p.Val367= Benign same residue
RELT p.Ala314= Likely benign same condition
RELT p.Arg338Pro Likely benign same condition
RELT p.Met363Val Benign same condition
RELT p.Pro201= Benign same condition
RELT p.Thr256Met Benign same condition
RELT p.Thr360= Benign same condition
RELT p.Ala160= Likely benign ★★ same type

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-val367glu (accessed [today's date]).

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