Is MIDEAS p.Ala970Val (c.2909C>T) pathogenic?

MIDEAS p.Ala970Val (c.2909C>T) is classified Uncertain significance in MIDEAS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.1908); Ultra-rare (popmax 0.0184%, nfe).

How common is MIDEAS p.Ala970Val (c.2909C>T) in the general population?

MIDEAS p.Ala970Val (c.2909C>T) is ultra-rare (popmax 0.0184%, nfe) (gnomAD).

What do computational predictors say about MIDEAS p.Ala970Val (c.2909C>T)?

AlphaMissense predicts likely benign (score 0.1908) — an in-silico prediction, not a clinical call.

MIDEAS p.Ala970Val

c.2909C>T · VCV3294821

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1908	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.06	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 11 kb · p 2.8e-05 · regional, not allelic
Overall
CADD	20.4	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 0.0184% European (non-Finnish) · 217/1,180,032 alleles

Filtering AF 0.0164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.0138% 222/1,613,486 alleles · ultra-rare exomes 203/1,461,334 · genomes 19/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0184%	5,438
Remaining individualsnot grpmax-eligible	0.008%	12,496

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: MIDEAS
Protein: p.Ala970Val
Coding: c.2909C>T
MANE Select: NM_001367710
Type: single nucleotide variant
Location: chr14:73721325 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 48.77 · 3 PDB
Residue 970: the 'disordered' region

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

Similar variants

MIDEAS c.2162+1G>A Uncertain significance ★ same type
MIDEAS p.Ala1001Val Uncertain significance ★ ⚠ same type
MIDEAS p.Ala170Val Uncertain significance ★ ⚠ same type
MIDEAS p.Ala203Thr Uncertain significance ★ ⚠ same type
MIDEAS p.Ala324Asp Uncertain significance ★ ⚠ same type
MIDEAS p.Ala55Glu Uncertain significance ★ ⚠ same type
MIDEAS p.Ala55Thr Uncertain significance ★ ⚠ same type
MIDEAS p.Ala620Thr 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/mideas-p-ala970val (accessed [today's date]).

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