Is MIF p.Ser75Phe (c.224C>T) pathogenic?

MIF p.Ser75Phe (c.224C>T) is classified Likely benign in MIF (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.2024); Rare (popmax 0.52%, mid); Associated with MIF-related disorder.

What condition is associated with MIF p.Ser75Phe (c.224C>T)?

MIF p.Ser75Phe (c.224C>T) is associated with MIF-related disorder (ClinVar).

How common is MIF p.Ser75Phe (c.224C>T) in the general population?

MIF p.Ser75Phe (c.224C>T) is rare (popmax 0.52%, mid) (gnomAD).

What do computational predictors say about MIF p.Ser75Phe (c.224C>T)?

AlphaMissense predicts likely benign (score 0.2024) — an in-silico prediction, not a clinical call.

MIF p.Ser75Phe

c.224C>T · rs182012324 · VCV3049829

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2024 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.52%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MIF-related disorder

Computational evidence

Protein change
AlphaMissense	0.2024	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -9.59	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 3.7	GERP 0.51, phastCons 0.73
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.52% Middle Eastern · 31/5,960 alleles

Filtering AF 0.376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.328%

Overall 0.153% 2,370/1,553,982 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.52%	192
South Asian	0.196%	510
Finnishnot grpmax-eligible	0.188%	531
European (non-Finnish)	0.168%	594
Remaining individualsnot grpmax-eligible	0.104%	957
Admixed American	0.0598%	1,672
Ashkenazi Jewishnot grpmax-eligible	0.0418%	2,390
African / African-American	0.0353%	2,829

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.Ser75Phe
Coding: c.224C>T
MANE Select: NM_002415
dbSNP: rs182012324
Type: single nucleotide variant
Location: chr22:23894887 (GRCh38)
Gene constraint: LOEUF 1.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.60 · 119 PDB
Residue 75: an α-helix

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

Disease context

MIF-related disorder

Similar variants

MIF p.Ile68= 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-ser75phe (accessed [today's date]).

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