Is MFF p.Ala210= (c.630C>A) pathogenic?

MFF p.Ala210= (c.630C>A) is classified Benign/Likely benign in MFF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Low-frequency (popmax 4.38%, sas); Associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2.

What condition is associated with MFF p.Ala210= (c.630C>A)?

MFF p.Ala210= (c.630C>A) is associated with encephalopathy due to defective mitochondrial and peroxisomal fission 2 (ClinVar).

How common is MFF p.Ala210= (c.630C>A) in the general population?

MFF p.Ala210= (c.630C>A) is low-frequency (popmax 4.38%, sas) (gnomAD).

MFF p.Ala210=

c.630C>A · rs140009845 · VCV382150

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.38%, sas)

Conditions

encephalopathy due to defective mitochondrial and peroxisomal fission 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Overall
CADD	14.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.38% South Asian · 3,981/90,962 alleles

Filtering AF 4.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.22%

Overall 0.824% 13,304/1,613,630 alleles · low-frequency exomes 12,275/1,461,362 · genomes 1,029/152,268 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	4.38%	23
Middle Eastern	3.81%	26
Ashkenazi Jewishnot grpmax-eligible	3.16%	32
Remaining individualsnot grpmax-eligible	1.22%	82
Admixed American	0.799%	125
European (non-Finnish)	0.554%	181
Amishnot grpmax-eligible	0.329%	304
African / African-American	0.32%	313
Finnishnot grpmax-eligible	0.184%	542
East Asian	0.0423%	2,362

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.Ala210=
Coding: c.630C>A
MANE Select: NM_001277062
dbSNP: rs140009845
Type: single nucleotide variant
Location: chr2:227352544 (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

Disease context

encephalopathy due to defective mitochondrial and peroxisomal fission 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Encephalopathy due to mitochondrial and peroxisomal fission defect (Orphanet):

Onset: Childhood, Infancy, Neonatal

Similar variants

MFF p.Asp75Asn Uncertain significance ★★ ⚠ same condition
MFF p.Ile250Ser Uncertain significance ★★ ⚠ same condition
MFF p.Pro31Leu Benign/Likely benign ★★ same condition
MFF c.-40-841T>G Likely pathogenic ★ same condition
MFF c.-40-842G>T Likely pathogenic ★ same condition
MFF p.Ile226Met Uncertain significance ★ ⚠ same condition
MFF p.Pro113Thr Uncertain significance ★ ⚠ same condition
MFF p.Trp286Arg 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/mff-p-ala210 (accessed [today's date]).

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