Is MIF p.Ala28Val (c.83C>T) pathogenic?

MIF p.Ala28Val (c.83C>T) is classified Uncertain significance in MIF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.5); Very rare (popmax 0.00834%, amr).

How common is MIF p.Ala28Val (c.83C>T) in the general population?

MIF p.Ala28Val (c.83C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about MIF p.Ala28Val (c.83C>T)?

AlphaMissense predicts ambiguous (score 0.5) — an in-silico prediction, not a clinical call.

MIF p.Ala28Val

c.83C>T · rs766674911 · VCV2207622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Computational evidence

Protein change
AlphaMissense	0.5	ambiguous
REVEL	0.451	indeterminate
SaProt	LLR -12.55	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.68, phastCons 1
Overall
CADD	22.6	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 0.00834% Admixed American · 5/59,980 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,612,776 alleles · very rare exomes 4/1,460,576 · genomes 1/152,200 · joint denominator

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.Ala28Val
Coding: c.83C>T
MANE Select: NM_002415
dbSNP: rs766674911
Type: single nucleotide variant
Location: chr22:23894557 (GRCh38)
Gene constraint: LOEUF 1.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.60 · 119 PDB
Residue 28: an α-helix

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

Similar variants

MIF p.Ala28Thr Uncertain significance ★ same residue
MIF p.Ala58Thr 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
MIF p.Gly52Cys Uncertain significance ★ same type
MIF p.Gly69Asp 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-ala28val (accessed [today's date]).

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