Is MAP1LC3B p.Pro2Arg (c.5C>G) pathogenic?

MAP1LC3B p.Pro2Arg (c.5C>G) is classified Uncertain significance in MAP1LC3B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.3344); Very rare (popmax 0.00119%, nfe).

How common is MAP1LC3B p.Pro2Arg (c.5C>G) in the general population?

MAP1LC3B p.Pro2Arg (c.5C>G) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about MAP1LC3B p.Pro2Arg (c.5C>G)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

MAP1LC3B p.Pro2Arg

c.5C>G · rs762464327 · VCV2358122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -9.53	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 6.8	GERP 0.79, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 11 kb · p 0.72 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.00119% European (non-Finnish) · 13/1,096,438 alleles

Filtering AF 0.000662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00051%

Overall 0.000915% 13/1,420,170 alleles · very rare exomes 12/1,268,246 · genomes 1/151,924 · joint denominator

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: MAP1LC3B
Protein: p.Pro2Arg
Coding: c.5C>G
MANE Select: NM_022818
dbSNP: rs762464327
Type: single nucleotide variant
Location: chr16:87392432 (GRCh38)
Gene constraint: LOEUF 1.24 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.88 · 51 PDB

Full MAP1LC3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP1LC3B p.Arg24Pro Uncertain significance ★ ⚠ same type
MAP1LC3B p.Asn74Ser Uncertain significance ★ ⚠ same type
MAP1LC3B p.Asn84Lys Uncertain significance ★ ⚠ same type
MAP1LC3B p.Asp56Gly Uncertain significance ★ ⚠ same type
MAP1LC3B p.Gln15Arg Uncertain significance ★ ⚠ same type
MAP1LC3B p.Gln77Arg Uncertain significance ★ ⚠ same type
MAP1LC3B p.Glu102Lys Uncertain significance ★ ⚠ same type
MAP1LC3B p.His86Asp 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/map1lc3b-p-pro2arg (accessed [today's date]).

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