Is MID2 p.Ile103Ser (c.308T>G) pathogenic?

MID2 p.Ile103Ser (c.308T>G) is classified Uncertain significance in MID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-23). AlphaMissense: likely pathogenic (0.997); Very rare (popmax 0.00702%, afr); Associated with intellectual disability, X-linked 101.

What condition is associated with MID2 p.Ile103Ser (c.308T>G)?

MID2 p.Ile103Ser (c.308T>G) is associated with intellectual disability, X-linked 101 (ClinVar).

How common is MID2 p.Ile103Ser (c.308T>G) in the general population?

MID2 p.Ile103Ser (c.308T>G) is very rare (popmax 0.00702%, afr) (gnomAD).

What do computational predictors say about MID2 p.Ile103Ser (c.308T>G)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

MID2 p.Ile103Ser

c.308T>G · rs965572589 · VCV2442092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00702%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 101

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic · top 10% in MID2
REVEL	0.665	pathogenic-leaning
SaProt	LLR -10.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 101 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00702% African / African-American · 4/56,985 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000496% 6/1,209,712 alleles · very rare exomes 5/1,098,207 · genomes 1/111,505 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00702%	14,246
Remaining individualsnot grpmax-eligible	0.0021%	47,590
South Asian	0.00176%	56,743

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.Ile103Ser
Coding: c.308T>G
MANE Select: NM_012216
dbSNP: rs965572589
Type: single nucleotide variant
Location: chrX:107840973 (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.Ser60= Benign ★★ same condition
MID2 p.Arg164His 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-ile103ser (accessed [today's date]).

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