Is MFF p.Arg266Cys (c.796C>T) pathogenic?

MFF p.Arg266Cys (c.796C>T) is classified Uncertain significance in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-10). AlphaMissense: likely pathogenic (0.7916); Absent from gnomAD v4.1.

How common is MFF p.Arg266Cys (c.796C>T) in the general population?

MFF p.Arg266Cys (c.796C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MFF p.Arg266Cys (c.796C>T)?

AlphaMissense predicts likely pathogenic (score 0.7916) — an in-silico prediction, not a clinical call.

MFF p.Arg266Cys

c.796C>T · rs2076294224 · VCV1327652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7916 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7916	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -11.34	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	32.0	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R317C vs ClinVar R266C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MFF
Protein: p.Arg266Cys
Coding: c.796C>T
MANE Select: NM_001277062
dbSNP: rs2076294224
Type: single nucleotide variant
Location: chr2:227357037 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 64.74

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

Similar variants

MFF p.Arg128Trp Uncertain significance ★★ ⚠ same type
MFF p.Arg136Cys Uncertain significance ★★ ⚠ same type
MFF p.Arg136His Uncertain significance ★★ ⚠ same type
MFF p.Arg199His Uncertain significance ★★ ⚠ same type
MFF p.Arg6Gln Uncertain significance ★★ ⚠ same type
MFF p.Arg92His Uncertain significance ★★ ⚠ same type
MFF p.Asp75Asn Uncertain significance ★★ ⚠ same type
MFF p.Gln52His 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/mff-p-arg266cys (accessed [today's date]).

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