Is CD101 p.Leu443Pro (c.1328T>C) pathogenic?

CD101 p.Leu443Pro (c.1328T>C) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.4977); Ultra-rare (popmax 0.0802%, eas).

How common is CD101 p.Leu443Pro (c.1328T>C) in the general population?

CD101 p.Leu443Pro (c.1328T>C) is ultra-rare (popmax 0.0802%, eas) (gnomAD).

What do computational predictors say about CD101 p.Leu443Pro (c.1328T>C)?

AlphaMissense predicts ambiguous (score 0.4977) — an in-silico prediction, not a clinical call.

CD101 p.Leu443Pro

c.1328T>C · VCV4222480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0802%, eas)

Computational evidence

Protein change
AlphaMissense	0.4977	ambiguous
REVEL	0.465	indeterminate
SaProt	LLR -10.78	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	24.4	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 0.0802% East Asian · 36/44,880 alleles

Filtering AF 0.0595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00527% 85/1,614,230 alleles · ultra-rare exomes 68/1,461,858 · genomes 17/152,372 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0802%	1,247
South Asian	0.0329%	3,036
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.00333%	30,016
European (non-Finnish)	0.000169%	590,019

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: CD101
Protein: p.Leu443Pro
Coding: c.1328T>C
MANE Select: NM_001256106
Type: single nucleotide variant
Location: chr1:117017189 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 443: the ig-like c2-type 4 domain

Full CD101 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD101 p.Arg622His Benign ★★ same type
CD101 p.Arg933Gln Benign ★★ same type
CD101 p.Asn225Ser Benign ★★ same type
CD101 p.Leu362Pro Benign ★★ same type
CD101 p.Ser525Arg Benign ★★ same type
CD101 p.Ser985= Benign ★★ same type
CD101 p.Tyr651Asp Benign ★★ same type
CD101 p.Ala195Thr 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/cd101-p-leu443pro (accessed [today's date]).

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