Is MACF1 p.Asp4369Val (c.13106A>T) pathogenic?

MACF1 p.Asp4369Val (c.13106A>T) is classified Benign/Likely benign in MACF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-04). AlphaMissense: likely benign (0.0923); Very rare (popmax 0.00842%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Asp4369Val (c.13106A>T)?

MACF1 p.Asp4369Val (c.13106A>T) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Asp4369Val (c.13106A>T) in the general population?

MACF1 p.Asp4369Val (c.13106A>T) is very rare (popmax 0.00842%, nfe) (gnomAD).

What do computational predictors say about MACF1 p.Asp4369Val (c.13106A>T)?

AlphaMissense predicts likely benign (score 0.0923) — an in-silico prediction, not a clinical call.

MACF1 p.Asp4369Val

c.13106A>T · rs142318271 · VCV2050476

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0923 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00842%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0923	likely benign
REVEL	0.1	moderately 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 2.1	GERP -1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 93 kb · p 4.8e-14 · regional, not allelic
Overall
CADD	17.32	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 D4374V vs ClinVar D4369V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00842% European (non-Finnish) · 99/1,175,572 alleles

Filtering AF 0.00705% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00654%

Overall 0.0064% 103/1,608,932 alleles · very rare exomes 96/1,456,702 · genomes 7/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00842%	11,874
Remaining individualsnot grpmax-eligible	0.00321%	31,150
African / African-American	0.00267%	37,400

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.Asp4369Val
Coding: c.13106A>T
MANE Select: NM_001394062
dbSNP: rs142318271
Type: single nucleotide variant
Location: chr1:39372489 (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-asp4369val (accessed [today's date]).

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