Is MARCKS p.Pro72Ser (c.214C>T) pathogenic?

MARCKS p.Pro72Ser (c.214C>T) is classified Uncertain significance in MARCKS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.0926); Absent from gnomAD v4.1.

How common is MARCKS p.Pro72Ser (c.214C>T) in the general population?

MARCKS p.Pro72Ser (c.214C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MARCKS p.Pro72Ser (c.214C>T)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

MARCKS p.Pro72Ser

c.214C>T · rs1774852125 · VCV2610717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,379,508)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -8.28	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 0.5	GERP -0.47, phastCons 0.99
Regional constraint	o/e 1.31	unconstrained · MANE · 2,830 bp · p 9e-12 · regional, not allelic
Overall
CADD	17.39	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

No allele count reported in gnomAD v4.1 (AN 1,379,508). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MARCKS
Protein: p.Pro72Ser
Coding: c.214C>T
MANE Select: NM_002356
dbSNP: rs1774852125
Type: single nucleotide variant
Location: chr6:113859794 (GRCh38)
Gene constraint: LOEUF 1.86 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.42 · 1 PDB
Residue 72: 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-pro72ser (accessed [today's date]).

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