Is MACF1 p.Ser7462Phe (c.22385C>T) pathogenic?

MACF1 p.Ser7462Phe (c.22385C>T) is classified Likely benign in MACF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-25). AlphaMissense: likely benign (0.1904); Rare (popmax 0.122%, sas); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Ser7462Phe (c.22385C>T)?

MACF1 p.Ser7462Phe (c.22385C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Ser7462Phe (c.22385C>T) in the general population?

MACF1 p.Ser7462Phe (c.22385C>T) is rare (popmax 0.122%, sas) (gnomAD).

What do computational predictors say about MACF1 p.Ser7462Phe (c.22385C>T)?

AlphaMissense predicts likely benign (score 0.1904) — an in-silico prediction, not a clinical call.

MACF1 p.Ser7462Phe

c.22385C>T · rs202106473 · VCV2741019

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1904 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.122%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1904	likely benign
REVEL	0.206	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 5,804 bp · p 0.0067 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S7295F vs ClinVar S7462F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.122% South Asian · 111/91,078 alleles

Filtering AF 0.103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0965%

Overall 0.00762% 123/1,614,180 alleles · rare exomes 116/1,461,866 · genomes 7/152,314 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.122%	821
Remaining individualsnot grpmax-eligible	0.016%	6,251
European (non-Finnish)	0.000169%	590,009

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: MACF1
Protein: p.Ser7462Phe
Coding: c.22385C>T
MANE Select: NM_001394062
dbSNP: rs202106473
Type: single nucleotide variant
Location: chr1:39484704 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)

Full MACF1 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

MACF1 p.Ser7462= Benign ★★ same residue
MACF1 p.Ala5598Ser Uncertain significance ★★ same condition
MACF1 p.Ala601Pro Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg30Gln Uncertain significance ★★ same condition
MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg4674Cys Uncertain significance ★★ same condition
MACF1 p.Arg5490Gln Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg5875Cys 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/macf1-p-ser7462phe (accessed [today's date]).

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