Is MFF p.Arg290His (c.869G>A) pathogenic?

MFF p.Arg290His (c.869G>A) is classified Uncertain significance in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-24). AlphaMissense: ambiguous (0.4941); Very rare (popmax 0.00534%, afr).

How common is MFF p.Arg290His (c.869G>A) in the general population?

MFF p.Arg290His (c.869G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about MFF p.Arg290His (c.869G>A)?

AlphaMissense predicts ambiguous (score 0.4941) — an in-silico prediction, not a clinical call.

MFF p.Arg290His

c.869G>A · rs62190918 · VCV1329809

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Computational evidence

Protein change
AlphaMissense	0.4941	ambiguous
REVEL	0.492	indeterminate
SaProt	LLR -10.98	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R341H vs ClinVar R290H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,840 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00248% 40/1,611,442 alleles · very rare exomes 35/1,459,250 · genomes 5/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,710
East Asian	0.00446%	22,439
Remaining individualsnot grpmax-eligible	0.00321%	31,139
European (non-Finnish)	0.00254%	39,325
South Asian	0.0022%	45,460

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: MFF
Protein: p.Arg290His
Coding: c.869G>A
MANE Select: NM_001277062
dbSNP: rs62190918
Type: single nucleotide variant
Location: chr2:227357110 (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.Arg290Gly Uncertain significance ★ ⚠ same residue
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

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-arg290his (accessed [today's date]).

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