Is MACF1 p.Arg30Trp (c.88C>T) pathogenic?

MACF1 p.Arg30Trp (c.88C>T) is classified Likely benign in MACF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.7264); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Arg30Trp (c.88C>T)?

MACF1 p.Arg30Trp (c.88C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Arg30Trp (c.88C>T) in the general population?

MACF1 p.Arg30Trp (c.88C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about MACF1 p.Arg30Trp (c.88C>T)?

AlphaMissense predicts likely pathogenic (score 0.7264) — an in-silico prediction, not a clinical call.

MACF1 p.Arg30Trp

c.88C>T · VCV4102086

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7264	likely pathogenic
REVEL	0.31	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -0.36, phastCons 1
Overall
CADD	20.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,002 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000929% 15/1,613,862 alleles · very rare exomes 14/1,461,658 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,001
South Asian	0.00329%	30,364
European (non-Finnish)	0.000847%	118,000

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.Arg30Trp
Coding: c.88C>T
MANE Select: NM_001394062 · reported on NM_012090
Type: single nucleotide variant
Location: chr1:39084306 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)
Residue 30: the 'actin-binding' region; the 'disordered' region

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.Arg30Gln Uncertain significance ★★ same residue
MACF1 p.Ala5598Ser Uncertain significance ★★ same condition
MACF1 p.Ala601Pro 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-arg30trp (accessed [today's date]).

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