Is MID1 p.Ala196= (c.588C>G) pathogenic?

MID1 p.Ala196= (c.588C>G) is classified Benign/Likely benign in MID1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.263%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MID1 p.Ala196= (c.588C>G)?

MID1 p.Ala196= (c.588C>G) is associated with Inborn genetic diseases (ClinVar).

How common is MID1 p.Ala196= (c.588C>G) in the general population?

MID1 p.Ala196= (c.588C>G) is rare (popmax 0.263%, nfe) (gnomAD).

MID1 p.Ala196=

c.588C>G · rs41303167 · VCV195070

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.263%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	13.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.263% European (non-Finnish) · 2,356/895,214 alleles

Filtering AF 0.254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.251%

Overall 0.221% 2,673/1,210,045 alleles · rare exomes 2,463/1,098,204 · genomes 210/111,841 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.345%	290
European (non-Finnish)grpmax	0.263%	380
Middle Eastern	0.253%	396
Remaining individualsnot grpmax-eligible	0.185%	541
Finnishnot grpmax-eligible	0.184%	542
Admixed American	0.048%	2,081
South Asian	0.0405%	2,470
African / African-American	0.0192%	5,195

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: MID1
Protein: p.Ala196=
Coding: c.588C>G
MANE Select: NM_000381
dbSNP: rs41303167
Type: single nucleotide variant
Location: chrX:10566960 (GRCh38)
Structure: AlphaFold pLDDT 86.51 · 5 PDB
Residue 196: an α-helix

Full MID1 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

MID1 p.Ala211Pro Uncertain significance ★★ ⚠ same condition
MID1 p.Arg291Thr Uncertain significance ★★ ⚠ same condition
MID1 p.Arg472Cys Uncertain significance ★★ ⚠ same condition
MID1 p.Asn234Lys Uncertain significance ★★ ⚠ same condition
MID1 p.Asp180Asn Uncertain significance ★★ ⚠ same condition
MID1 p.Gly529Ala Uncertain significance ★★ ⚠ same condition
MID1 p.Ser225Asn Uncertain significance ★★ ⚠ same condition
MID1 p.Thr393Ile 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/mid1-p-ala196 (accessed [today's date]).

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