Is MACF1 p.Cys810Phe (c.2429G>T) pathogenic?

MACF1 p.Cys810Phe (c.2429G>T) is classified Likely benign in MACF1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). AlphaMissense: ambiguous (0.5203); Rare (popmax 0.928%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Cys810Phe (c.2429G>T)?

MACF1 p.Cys810Phe (c.2429G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Cys810Phe (c.2429G>T) in the general population?

MACF1 p.Cys810Phe (c.2429G>T) is rare (popmax 0.928%, nfe) (gnomAD).

What do computational predictors say about MACF1 p.Cys810Phe (c.2429G>T)?

AlphaMissense predicts ambiguous (score 0.5203) — an in-silico prediction, not a clinical call.

MACF1 p.Cys810Phe

c.2429G>T · rs148207245 · VCV777558

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.5203 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.928%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5203	ambiguous
REVEL	0.704	pathogenic-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 39 kb · p 0.00039 · regional, not allelic
Overall
CADD	23.4	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 C815F vs ClinVar C810F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.928% European (non-Finnish) · 10,956/1,180,016 alleles

Filtering AF 0.914% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.908%

Overall 0.76% 12,264/1,614,104 alleles · rare exomes 11,508/1,461,868 · genomes 756/152,236 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.09%	48
European (non-Finnish)grpmax	0.928%	108
Remaining individualsnot grpmax-eligible	0.64%	156
Ashkenazi Jewishnot grpmax-eligible	0.52%	192
South Asian	0.327%	306
Finnishnot grpmax-eligible	0.292%	342
Admixed American	0.247%	406
African / African-American	0.127%	790
Middle Eastern	0.099%	1,010
East Asian	0.00223%	44,882

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys810Phe
Coding: c.2429G>T
MANE Select: NM_001394062
dbSNP: rs148207245
Type: single nucleotide variant
Location: chr1:39297693 (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.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
MACF1 p.Arg6864Gln 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-cys810phe (accessed [today's date]).

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