Is MID2 p.Ser60= (c.180A>C) pathogenic?

MID2 p.Ser60= (c.180A>C) is classified Benign in MID2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-09-05). Common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, X-linked 101.

What condition is associated with MID2 p.Ser60= (c.180A>C)?

MID2 p.Ser60= (c.180A>C) is associated with intellectual disability, X-linked 101 (ClinVar).

MID2 p.Ser60=

Q: How common is MID2 p.Ser60= (c.180A>C) in the general population?

MID2 p.Ser60= (c.180A>C) is common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.180A>C · rs2236083 · VCV1321169

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 19.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, X-linked 101

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.5	GERP -3.5
Overall
CADD	0.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.6% African / African-American · 11,131/56,870 alleles

Filtering AF 19.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.1%

Overall 6.98% 84,457/1,209,290 alleles · common exomes 73,308/1,098,216 · genomes 11,149/111,074 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	22.8%	4
African / African-Americangrpmax	19.6%	5
East Asian	10.8%	9
Middle Eastern	10.8%	9
South Asian	8.95%	11
Remaining individualsnot grpmax-eligible	7.89%	13
Finnishnot grpmax-eligible	6.91%	14
European (non-Finnish)	5.96%	17
Admixed American	5.67%	18
Ashkenazi Jewishnot grpmax-eligible	4.92%	20

Amish 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: MID2
Protein: p.Ser60=
Coding: c.180A>C
MANE Select: NM_012216
dbSNP: rs2236083
Type: single nucleotide variant
Location: chrX:107840845 (GRCh38)
Structure: AlphaFold pLDDT 80.18 · 4 PDB

Full MID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, X-linked 101 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MID2 p.Ala150Ser Uncertain significance ★★ ⚠ same condition
MID2 p.Arg164His Uncertain significance ★ same condition
MID2 p.Ile103Ser Uncertain significance ★ ⚠ same condition
MID2 p.Thr125Ala Uncertain significance ★ ⚠ same condition
MID2 p.Arg121His Uncertain significance ★★ ⚠ same type
MID2 p.Arg164Gly Uncertain significance ★★ ⚠ same type
MID2 p.Thr194= Benign/Likely benign ★★ same type
MID2 p.Arg105Pro 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/mid2-p-ser60 (accessed [today's date]).

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