Is REL p.Thr401Ala (c.1201A>G) pathogenic?

REL p.Thr401Ala (c.1201A>G) is classified Benign/Likely benign in REL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-31). AlphaMissense: likely benign (0.0677); Low-frequency (popmax 2.09%, sas).

How common is REL p.Thr401Ala (c.1201A>G) in the general population?

REL p.Thr401Ala (c.1201A>G) is low-frequency (popmax 2.09%, sas) (gnomAD).

What do computational predictors say about REL p.Thr401Ala (c.1201A>G)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

REL p.Thr401Ala

c.1201A>G · rs140572082 · VCV724129

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.09%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.57	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 -0.71	GERP -2.8
Regional constraint	o/e 1.00	unconstrained · MANE · 1,945 bp · p 0.96 · regional, not allelic
Overall
CADD	2.354	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM T433A vs ClinVar T401A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.09% South Asian · 1,902/91,088 alleles

Filtering AF 2.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.98%

Overall 0.15% 2,417/1,614,210 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.09%	48
Middle Eastern	0.594%	168
Remaining individualsnot grpmax-eligible	0.176%	568
European (non-Finnish)	0.0295%	3,391
Admixed American	0.025%	4,002
African / African-American	0.00666%	15,009
East Asian	0.00223%	44,882

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: REL
Protein: p.Thr401Ala
Coding: c.1201A>G
MANE Select: NM_001291746
dbSNP: rs140572082
Type: single nucleotide variant
Location: chr2:60921972 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.46
Residue 401: the 'disordered' region

Full REL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

REL p.Thr401Ile Likely benign ★ same residue
REL p.Asp224Asn Uncertain significance ★★ ⚠ same type
REL p.Gln503His Uncertain significance ★★ ⚠ same type
REL p.Leu298Val Uncertain significance ★★ ⚠ same type
REL p.Met372Lys Uncertain significance ★★ ⚠ same type
REL p.Met372Val Uncertain significance ★★ ⚠ same type
REL p.Phe559Leu Uncertain significance ★★ ⚠ same type
REL p.Ser556Gly Uncertain significance ★★ ⚠ 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/rel-p-thr401ala (accessed [today's date]).

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