Is COLEC11 p.Pro103Ser (c.307C>T) pathogenic?

COLEC11 p.Pro103Ser (c.307C>T) is classified Uncertain significance in COLEC11 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-11). AlphaMissense: likely benign (0.0955); Ultra-rare (popmax 0.0684%, amr); Associated with 3MC syndrome 2.

What condition is associated with COLEC11 p.Pro103Ser (c.307C>T)?

COLEC11 p.Pro103Ser (c.307C>T) is associated with 3MC syndrome 2 (ClinVar).

How common is COLEC11 p.Pro103Ser (c.307C>T) in the general population?

COLEC11 p.Pro103Ser (c.307C>T) is ultra-rare (popmax 0.0684%, amr) (gnomAD).

What do computational predictors say about COLEC11 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

COLEC11 p.Pro103Ser

c.307C>T · rs773032227 · VCV1028290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0684%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

3MC syndrome 2

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 40 kb · p 0.00019 · regional, not allelic
Overall
CADD	22.2	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 0.0684% Admixed American · 41/59,974 alleles

Filtering AF 0.0518% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0459%

Overall 0.00257% 41/1,597,458 alleles · ultra-rare exomes 38/1,445,344 · genomes 3/152,114 · 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: COLEC11
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_024027
dbSNP: rs773032227
Type: single nucleotide variant
Location: chr2:3640310 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.64 · 3 PDB
Residue 103: the collagen-like domain; the 'disordered' region

Full COLEC11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3MC syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COLEC11 p.Pro103Ala Uncertain significance ★ ⚠ same residue
COLEC11 p.Gly204Ser Pathogenic ★ same condition
COLEC11 p.Ala166Thr Uncertain significance ★ ⚠ same condition
COLEC11 p.Arg147His Uncertain significance ★ ⚠ same condition
COLEC11 p.Cys170Arg Uncertain significance ★ ⚠ same condition
COLEC11 p.Gly145Ser Uncertain significance ★ ⚠ same condition
COLEC11 p.Gly95Val Uncertain significance ★ ⚠ same condition
COLEC11 p.Thr64= Conflicting classifications of pathogenicity ★ same condition

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/colec11-p-pro103ser (accessed [today's date]).

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