Is MFF p.Ser67Pro (c.199T>C) pathogenic?

MFF p.Ser67Pro (c.199T>C) is classified Likely benign in MFF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). AlphaMissense: likely benign (0.0533); Very rare (popmax 0.00348%, amr); Associated with Inborn genetic diseases.

What condition is associated with MFF p.Ser67Pro (c.199T>C)?

MFF p.Ser67Pro (c.199T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MFF p.Ser67Pro (c.199T>C) in the general population?

MFF p.Ser67Pro (c.199T>C) is very rare (popmax 0.00348%, amr) (gnomAD).

What do computational predictors say about MFF p.Ser67Pro (c.199T>C)?

AlphaMissense predicts likely benign (score 0.0533) — an in-silico prediction, not a clinical call.

MFF p.Ser67Pro

c.199T>C · rs1174550579 · VCV2402967

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00348%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0533	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.17, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 26 kb · p 0.33 · regional, not allelic
Overall
CADD	15.63	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 S93P vs ClinVar S67P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00348% Admixed American · 2/57,540 alleles

Filtering AF 0.000577% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.000125% 2/1,606,092 alleles · very rare exomes 2/1,453,756 · genomes 0/152,336 · 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: MFF
Protein: p.Ser67Pro
Coding: c.199T>C
MANE Select: NM_001277062
dbSNP: rs1174550579
Type: single nucleotide variant
Location: chr2:227332436 (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

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

Similar variants

MFF p.Arg128Trp Uncertain significance ★★ ⚠ same condition
MFF p.Arg136His Uncertain significance ★★ ⚠ same condition
MFF p.Arg6Gln Uncertain significance ★★ ⚠ same condition
MFF p.Arg92His Uncertain significance ★★ ⚠ same condition
MFF p.Gln52His Uncertain significance ★★ ⚠ same condition
MFF p.His215Pro Uncertain significance ★★ ⚠ same condition
MFF p.Ile230Thr Uncertain significance ★★ ⚠ same condition
MFF p.Ile250Ser 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-ser67pro (accessed [today's date]).

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