Is MIF p.Ile68= (c.204C>A) pathogenic?

MIF p.Ile68= (c.204C>A) is classified Likely benign in MIF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-08). Rare (popmax 0.117%, amr); Associated with MIF-related disorder.

What condition is associated with MIF p.Ile68= (c.204C>A)?

MIF p.Ile68= (c.204C>A) is associated with MIF-related disorder (ClinVar).

How common is MIF p.Ile68= (c.204C>A) in the general population?

MIF p.Ile68= (c.204C>A) is rare (popmax 0.117%, amr) (gnomAD).

MIF p.Ile68=

c.204C>A · rs754953765 · VCV3035802

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.117%, amr)

Conditions

MIF-related disorder

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 -0.067	GERP -3.1, phastCons 0.48
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.117% Admixed American · 61/52,050 alleles

Filtering AF 0.0936% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.085%

Overall 0.00393% 61/1,553,012 alleles · rare

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: MIF
Protein: p.Ile68=
Coding: c.204C>A
MANE Select: NM_002415
dbSNP: rs754953765
Type: single nucleotide variant
Location: chr22:23894867 (GRCh38)
Gene constraint: LOEUF 1.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.60 · 119 PDB

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

Disease context

MIF-related disorder

Similar variants

MIF p.Ser75Phe Likely benign same condition
MIF p.Ala58Thr Uncertain significance ★★ ⚠ same type
MIF p.Ala28Thr Uncertain significance ★ same type
MIF p.Ala28Val Uncertain significance ★ same type
MIF p.Ala71Pro Uncertain significance ★ ⚠ same type
MIF p.Arg74Gly Uncertain significance ★ ⚠ same type
MIF p.Arg74Leu Uncertain significance ★ ⚠ same type
MIF p.Asn111Thr 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/mif-p-ile68 (accessed [today's date]).

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