Is MAP1B p.Glu692Lys (c.2074G>A) pathogenic?

MAP1B p.Glu692Lys (c.2074G>A) is classified Uncertain significance in MAP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: ambiguous (0.3463); Very rare (popmax 0.00207%, amr).

How common is MAP1B p.Glu692Lys (c.2074G>A) in the general population?

MAP1B p.Glu692Lys (c.2074G>A) is very rare (popmax 0.00207%, amr) (gnomAD).

What do computational predictors say about MAP1B p.Glu692Lys (c.2074G>A)?

AlphaMissense predicts ambiguous (score 0.3463) — an in-silico prediction, not a clinical call.

MAP1B p.Glu692Lys

c.2074G>A · VCV3383714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3463 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00207%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3463	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -9.56	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 5,330 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	22.4	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 0.00207% Admixed American · 1/48,356 alleles

Overall 0.000193% 3/1,556,558 alleles · very rare exomes 3/1,408,304 · genomes 0/148,254 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00207%	48,356
African / African-American	0.00141%	70,820
European (non-Finnish)	8.65e-05%	1,155,852

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.Glu692Lys
Coding: c.2074G>A
MANE Select: NM_005909
Type: single nucleotide variant
Location: chr5:72195429 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 692: the 'disordered' region; a UniProt-annotated variant site (in pvnh9)

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

Similar variants

MAP1B p.Arg1664Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg2140Ter Pathogenic ★★ same type
MAP1B p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg85Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Arg999Ter Pathogenic/Likely pathogenic ★★ same type
MAP1B p.Ala966Val Uncertain significance ★★ ⚠ same type
MAP1B p.Arg1399Cys Uncertain significance ★★ ⚠ same type
MAP1B p.Arg1948Trp 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/map1b-p-glu692lys (accessed [today's date]).

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