Is MARCKS p.Ala306Asp (c.917C>A) pathogenic?

MARCKS p.Ala306Asp (c.917C>A) is classified Uncertain significance in MARCKS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely benign (0.2532); Very rare (popmax 0.00239%, nfe).

How common is MARCKS p.Ala306Asp (c.917C>A) in the general population?

MARCKS p.Ala306Asp (c.917C>A) is very rare (popmax 0.00239%, nfe) (gnomAD).

What do computational predictors say about MARCKS p.Ala306Asp (c.917C>A)?

AlphaMissense predicts likely benign (score 0.2532) — an in-silico prediction, not a clinical call.

MARCKS p.Ala306Asp

c.917C>A · rs774461693 · VCV2549456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2532 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00239%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2532	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.57, phastCons 0.91
Regional constraint	o/e 1.31	unconstrained · MANE · 2,830 bp · p 9e-12 · regional, not allelic
Overall
CADD	17.92	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% European (non-Finnish) · 27/1,131,910 alleles

Filtering AF 0.00163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.00185% 28/1,516,170 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00239%	41,923
Remaining individualsnot grpmax-eligible	0.00174%	57,350

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: MARCKS
Protein: p.Ala306Asp
Coding: c.917C>A
MANE Select: NM_002356
dbSNP: rs774461693
Type: single nucleotide variant
Location: chr6:113860497 (GRCh38)
Gene constraint: LOEUF 1.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.42 · 1 PDB
Residue 306: the 'disordered' region

Full MARCKS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MARCKS p.Ala100Asp Uncertain significance ★ ⚠ same type
MARCKS p.Ala142Asp Uncertain significance ★ ⚠ same type
MARCKS p.Ala184Val Uncertain significance ★ ⚠ same type
MARCKS p.Ala201Asp Uncertain significance ★ ⚠ same type
MARCKS p.Ala201Val Uncertain significance ★ ⚠ same type
MARCKS p.Ala203Val Uncertain significance ★ ⚠ same type
MARCKS p.Ala209Val Uncertain significance ★ ⚠ same type
MARCKS p.Ala217Val Uncertain significance ★ ⚠ same type

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/marcks-p-ala306asp (accessed [today's date]).

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