Is MAP1B p.Arg1224Cys (c.3670C>T) pathogenic?

MAP1B p.Arg1224Cys (c.3670C>T) is classified Likely benign in MAP1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0928); Ultra-rare (popmax 0.011%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAP1B p.Arg1224Cys (c.3670C>T)?

MAP1B p.Arg1224Cys (c.3670C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAP1B p.Arg1224Cys (c.3670C>T) in the general population?

MAP1B p.Arg1224Cys (c.3670C>T) is ultra-rare (popmax 0.011%, nfe) (gnomAD).

What do computational predictors say about MAP1B p.Arg1224Cys (c.3670C>T)?

AlphaMissense predicts likely benign (score 0.0928) — an in-silico prediction, not a clinical call.

MAP1B p.Arg1224Cys

c.3670C>T · rs777754669 · VCV2210730

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0928	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.36	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 4	GERP 0.28, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% European (non-Finnish) · 130/1,180,038 alleles

Filtering AF 0.00944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00905% 146/1,614,052 alleles · ultra-rare exomes 140/1,461,872 · genomes 6/152,180 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)grpmax	0.011%	9,077
Admixed American	0.00833%	12,001
African / African-American	0.00133%	74,916
South Asian	0.0011%	91,084

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MAP1B
Protein: p.Arg1224Cys
Coding: c.3670C>T
MANE Select: NM_005909
dbSNP: rs777754669
Type: single nucleotide variant
Location: chr5:72197025 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1224: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression)

Full MAP1B 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

MAP1B p.Arg1224= Likely benign ★ same residue
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1480Tyr Uncertain significance ★★ ⚠ same condition
MAP1B p.Asp1993Gly Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu1944Lys Uncertain significance ★★ ⚠ same condition
MAP1B p.Glu2435Val Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly919Arg Uncertain significance ★★ ⚠ same condition
MAP1B p.Gly932Ser 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/map1b-p-arg1224cys (accessed [today's date]).

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