Is MAP1B p.Phe1838Leu (c.5512T>C) pathogenic?

MAP1B p.Phe1838Leu (c.5512T>C) is classified Benign/Likely benign in MAP1B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). AlphaMissense: ambiguous (0.431); Low-frequency (popmax 1.06%, amr).

How common is MAP1B p.Phe1838Leu (c.5512T>C) in the general population?

MAP1B p.Phe1838Leu (c.5512T>C) is low-frequency (popmax 1.06%, amr) (gnomAD).

What do computational predictors say about MAP1B p.Phe1838Leu (c.5512T>C)?

AlphaMissense predicts ambiguous (score 0.431) — an in-silico prediction, not a clinical call.

MAP1B p.Phe1838Leu

c.5512T>C · rs139319889 · VCV791395

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.431 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.431	ambiguous
REVEL	0.101	moderately benign-leaning
SaProt	LLR -4.73	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 6.2	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	20.4	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 1.06% Admixed American · 639/60,034 alleles

Filtering AF 0.996% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.969%

Overall 0.0803% 1,296/1,614,250 alleles · low-frequency exomes 1,037/1,461,892 · genomes 259/152,358 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	1.06%	94
East Asian	0.475%	211
Remaining individualsnot grpmax-eligible	0.123%	812
South Asian	0.0867%	1,153
Finnishnot grpmax-eligible	0.0828%	1,208
African / African-American	0.0413%	2,421
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.0171%	5,842

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.Phe1838Leu
Coding: c.5512T>C
MANE Select: NM_005909
dbSNP: rs139319889
Type: single nucleotide variant
Location: chr5:72198867 (GRCh38)
Gene constraint: LOEUF 0.105 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.18
Residue 1838: a UniProt-annotated variant site (in pvnh9); a UniProt-annotated variant site (in pvnh9; no effect on protein expression); a UniProt-annotated variant site (in)

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

Similar variants

MAP1B p.Phe1838Ile Uncertain significance ★★ ⚠ same residue
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

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-phe1838leu (accessed [today's date]).

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