Is ME3 p.Pro38Ser (c.112C>T) pathogenic?

ME3 p.Pro38Ser (c.112C>T) is classified Uncertain significance in ME3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). AlphaMissense: likely benign (0.0711); Very rare (popmax 8.53e-05%, nfe).

How common is ME3 p.Pro38Ser (c.112C>T) in the general population?

ME3 p.Pro38Ser (c.112C>T) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

What do computational predictors say about ME3 p.Pro38Ser (c.112C>T)?

AlphaMissense predicts likely benign (score 0.0711) — an in-silico prediction, not a clinical call.

ME3 p.Pro38Ser

c.112C>T · rs2496963367 · VCV3124765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0711	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.21	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 -0.7	GERP -4.3
Regional constraint	o/e 0.85	unconstrained · MANE · 231 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	0.065	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 8.53e-05% European (non-Finnish) · 1/1,172,732 alleles

Overall 6.94e-05% 1/1,441,770 alleles · very rare

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: ME3
Protein: p.Pro38Ser
Coding: c.112C>T
MANE Select: NM_001161586
dbSNP: rs2496963367
Type: single nucleotide variant
Location: chr11:86671833 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.20 · 7 PDB
Residue 38: the 'disordered' region

Full ME3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ME3 p.Pro38Leu Uncertain significance ★ ⚠ same residue
ME3 p.Ala21Thr Uncertain significance ★ ⚠ same type
ME3 p.Ala29Glu Uncertain significance ★ ⚠ same type
ME3 p.Ala420Asp Uncertain significance ★ same type
ME3 p.Arg10Trp Uncertain significance ★ ⚠ same type
ME3 p.Arg190Cys Uncertain significance ★ ⚠ same type
ME3 p.Arg24Pro Uncertain significance ★ ⚠ same type
ME3 p.Arg289His 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/me3-p-pro38ser (accessed [today's date]).

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