Is MACF1 p.Val931= (c.2793C>T) pathogenic?

MACF1 p.Val931= (c.2793C>T) is classified Benign/Likely benign in MACF1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-05). Low-frequency (popmax 3.36%, afr); Associated with lissencephaly 9 with complex brainstem malformation.

What condition is associated with MACF1 p.Val931= (c.2793C>T)?

MACF1 p.Val931= (c.2793C>T) is associated with lissencephaly 9 with complex brainstem malformation (ClinVar).

How common is MACF1 p.Val931= (c.2793C>T) in the general population?

MACF1 p.Val931= (c.2793C>T) is low-frequency (popmax 3.36%, afr) (gnomAD).

MACF1 p.Val931=

c.2793C>T · rs74718295 · VCV1619756

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.36%, afr)

Conditions

lissencephaly 9 with complex brainstem malformation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.42	GERP -3, phastCons 0.98
Overall
CADD	9.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.36% African / African-American · 2,518/75,000 alleles

Filtering AF 3.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.2%

Overall 0.179% 2,882/1,613,938 alleles · low-frequency exomes 1,381/1,461,694 · genomes 1,501/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.36%	30
Remaining individualsnot grpmax-eligible	0.259%	386
Admixed American	0.228%	438
Middle Eastern	0.099%	1,010
South Asian	0.00879%	11,380
European (non-Finnish)	0.00424%	23,599
East Asian	0.00223%	44,876

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.Val931=
Coding: c.2793C>T
MANE Select: NM_001394062
dbSNP: rs74718295
Type: single nucleotide variant
Location: chr1:39309573 (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

lissencephaly 9 with complex brainstem malformation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MACF1 p.Arg7251Pro Likely pathogenic ★★ same condition
MACF1 p.Arg30Gln Uncertain significance ★★ same condition
MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg6864Gln Uncertain significance ★★ same condition
MACF1 p.Arg7005Trp Uncertain significance ★★ ⚠ same condition
MACF1 p.Glu6915Lys Uncertain significance ★★ same condition
MACF1 p.Ile380Thr Uncertain significance ★★ ⚠ same condition
MACF1 p.Leu6865Phe 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-val931 (accessed [today's date]).

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