Is MDFIC p.Cys201Arg (c.601T>C) pathogenic?

MDFIC p.Cys201Arg (c.601T>C) is classified Uncertain significance in MDFIC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.9131); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with MDFIC p.Cys201Arg (c.601T>C)?

MDFIC p.Cys201Arg (c.601T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MDFIC p.Cys201Arg (c.601T>C) in the general population?

MDFIC p.Cys201Arg (c.601T>C) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about MDFIC p.Cys201Arg (c.601T>C)?

AlphaMissense predicts likely pathogenic (score 0.9131) — an in-silico prediction, not a clinical call.

MDFIC p.Cys201Arg

c.601T>C · rs769748201 · VCV2406983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9131	likely pathogenic
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -13.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 93 kb · p 0.027 · regional, not allelic
Overall
CADD	29.2	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 0.0117% Admixed American · 7/60,026 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000434% 7/1,614,248 alleles · ultra-rare exomes 7/1,461,892 · genomes 0/152,356 · 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: MDFIC
Protein: p.Cys201Arg
Coding: c.601T>C
MANE Select: NM_001166345
dbSNP: rs769748201
Type: single nucleotide variant
Location: chr7:115015795 (GRCh38)
Gene constraint: LOEUF 1.501 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.05 · 5 PDB
Residue 201: the mdfi domain; a UniProt-annotated variant site (in lmphm12)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MDFIC c.-188G>C Uncertain significance ★ same condition
MDFIC c.-246C>T Uncertain significance ★ same condition
MDFIC c.-24G>T Uncertain significance ★ same condition
MDFIC c.-269T>A Uncertain significance ★ same condition
MDFIC c.-303G>A Uncertain significance ★ same condition
MDFIC c.-308C>A Uncertain significance ★ same condition
MDFIC c.-309G>A Uncertain significance ★ same condition
MDFIC c.-317T>A Uncertain significance ★ same condition

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/mdfic-p-cys201arg (accessed [today's date]).

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