Is MTCL1 p.Arg702Ser (c.2106G>T) pathogenic?

MTCL1 p.Arg702Ser (c.2106G>T) is classified Uncertain significance in MTCL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-02). AlphaMissense: likely pathogenic (0.6775); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MTCL1 p.Arg702Ser (c.2106G>T)?

MTCL1 p.Arg702Ser (c.2106G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTCL1 p.Arg702Ser (c.2106G>T) in the general population?

MTCL1 p.Arg702Ser (c.2106G>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about MTCL1 p.Arg702Ser (c.2106G>T)?

AlphaMissense predicts likely pathogenic (score 0.6775) — an in-silico prediction, not a clinical call.

MTCL1 p.Arg702Ser

c.2106G>T · rs376804537 · VCV2541978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6775	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	LLR -10.17	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.5, phastCons 1
Overall
CADD	23.3	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 0.000678% European (non-Finnish) · 8/1,180,038 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,608 alleles · very rare

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: MTCL1
Protein: p.Arg702Ser
Coding: c.2106G>T
MANE Select: NM_001395333
dbSNP: rs376804537
Type: single nucleotide variant
Location: chr18:8784138 (GRCh38)
Gene constraint: LOEUF 0.663 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.33

Full MTCL1 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

MTCL1 p.Thr562Ala Uncertain significance ★★ ⚠ same condition
MTCL1 p.Ala964Thr Likely benign ★★ same condition
MTCL1 p.Gly846Ala Likely benign ★★ same condition
MTCL1 p.Ile925Val Likely benign ★★ same condition
MTCL1 c.3939+3A>G Uncertain significance ★ same condition
MTCL1 p.Ala1013Val Uncertain significance ★ same condition
MTCL1 p.Ala1164Val Uncertain significance ★ ⚠ same condition
MTCL1 p.Ala1182Thr 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/mtcl1-p-arg702ser (accessed [today's date]).

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