Is MIP p.Ala7Val (c.20C>T) pathogenic?

MIP p.Ala7Val (c.20C>T) is classified Uncertain significance in MIP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-31). AlphaMissense: likely benign (0.0927); Ultra-rare (popmax 0.0267%, eas).

How common is MIP p.Ala7Val (c.20C>T) in the general population?

MIP p.Ala7Val (c.20C>T) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about MIP p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.0927) — an in-silico prediction, not a clinical call.

MIP p.Ala7Val

c.20C>T · rs201697509 · VCV1676377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0927 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0927	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -5.95	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 7.6	GERP -0.33, phastCons 1
Overall
CADD	19.91	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 0.0267% East Asian · 12/44,886 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000743% 12/1,614,122 alleles · ultra-rare exomes 9/1,461,786 · genomes 3/152,336 · joint denominator

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: MIP
Protein: p.Ala7Val
Coding: c.20C>T
MANE Select: NM_012064
dbSNP: rs201697509
Type: single nucleotide variant
Location: chr12:56454594 (GRCh38)
Structure: AlphaFold pLDDT 78.91

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

Similar variants

MIP c.606+1G>C Pathogenic/Likely pathogenic ★★ same type
MIP p.Arg33Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
MIP p.Trp205Ter Pathogenic ★★ same type
MIP p.Glu232Gln Uncertain significance ★★ ⚠ same type
MIP p.Gly165Ser Uncertain significance ★★ ⚠ same type
MIP p.Lys238Thr Uncertain significance ★★ ⚠ same type
MIP p.Thr108Ile Uncertain significance ★★ ⚠ same type
MIP p.Val142Met 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/mip-p-ala7val (accessed [today's date]).

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