Is RELT p.Arg338Pro (c.1013G>C) pathogenic?

RELT p.Arg338Pro (c.1013G>C) is classified Likely benign in RELT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-18). AlphaMissense: ambiguous (0.3429); Rare (popmax 0.365%, nfe); Associated with RELT-related disorder.

What condition is associated with RELT p.Arg338Pro (c.1013G>C)?

RELT p.Arg338Pro (c.1013G>C) is associated with RELT-related disorder (ClinVar).

How common is RELT p.Arg338Pro (c.1013G>C) in the general population?

RELT p.Arg338Pro (c.1013G>C) is rare (popmax 0.365%, nfe) (gnomAD).

What do computational predictors say about RELT p.Arg338Pro (c.1013G>C)?

AlphaMissense predicts ambiguous (score 0.3429) — an in-silico prediction, not a clinical call.

RELT p.Arg338Pro

c.1013G>C · rs147659360 · VCV3050139

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3429 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.365%, nfe)

Conditions

RELT-related disorder

Computational evidence

Protein change
AlphaMissense	0.3429	ambiguous
REVEL	0.507	indeterminate
SaProt	LLR -5.03	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 6,351 bp · p 0.12 · regional, not allelic
Overall
CADD	25.5	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 0.365% European (non-Finnish) · 4,301/1,179,924 alleles

Filtering AF 0.355% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.352%

Overall 0.313% 5,040/1,612,072 alleles · rare exomes 4,660/1,459,756 · genomes 380/152,316 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.53%	189
European (non-Finnish)grpmax	0.365%	274
Finnishnot grpmax-eligible	0.353%	283
Remaining individualsnot grpmax-eligible	0.294%	340
Admixed American	0.153%	652
South Asian	0.0538%	1,859
African / African-American	0.0466%	2,144
Middle Eastern	0.033%	3,031
East Asian	0.00223%	44,874

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg338Pro
Coding: c.1013G>C
MANE Select: NM_152222
dbSNP: rs147659360
Type: single nucleotide variant
Location: chr11:73394701 (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.Ala314= 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.Val367= Benign same condition
RELT p.Val367Glu 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-arg338pro (accessed [today's date]).

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