Is MAP1B p.Thr2423Ser (c.7268C>G) pathogenic?

MAP1B p.Thr2423Ser (c.7268C>G) is classified Uncertain significance in MAP1B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-03). AlphaMissense: likely pathogenic (0.8646); Very rare (popmax 0.00223%, eas).

How common is MAP1B p.Thr2423Ser (c.7268C>G) in the general population?

MAP1B p.Thr2423Ser (c.7268C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MAP1B p.Thr2423Ser (c.7268C>G)?

AlphaMissense predicts likely pathogenic (score 0.8646) — an in-silico prediction, not a clinical call.

MAP1B p.Thr2423Ser

c.7268C>G · VCV3389192

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8646 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8646	likely pathogenic
REVEL	0.361	indeterminate
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 5,431 bp · p 1.1e-08 · 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 0.00223% East Asian · 1/44,854 alleles

Overall 0.000124% 2/1,612,638 alleles · very rare exomes 2/1,460,638 · genomes 0/152,000 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,854
European (non-Finnish)	8.48e-05%	1,179,594

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.Thr2423Ser
Coding: c.7268C>G
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72205100 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 2423: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); the 'mediates interaction with tmem185a' region

Full MAP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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MAP1B p.Arg85Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same type
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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-thr2423ser (accessed [today's date]).

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