Is CD101 p.Asn556Asp (c.1666A>G) pathogenic?

CD101 p.Asn556Asp (c.1666A>G) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.0707); Rare (popmax 0.123%, nfe).

How common is CD101 p.Asn556Asp (c.1666A>G) in the general population?

CD101 p.Asn556Asp (c.1666A>G) is rare (popmax 0.123%, nfe) (gnomAD).

What do computational predictors say about CD101 p.Asn556Asp (c.1666A>G)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

CD101 p.Asn556Asp

c.1666A>G · rs145387761 · VCV2370835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -4.77	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 -0.33	GERP -3.5
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	0.259	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 0.123% European (non-Finnish) · 1,452/1,179,166 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0984% 1,587/1,612,862 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.123%	812
Admixed American	0.0768%	1,302
Remaining individualsnot grpmax-eligible	0.0592%	1,688
South Asian	0.0341%	2,934
Middle Eastern	0.033%	3,027
African / African-American	0.02%	5,001
Finnishnot grpmax-eligible	0.00469%	21,339
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,562

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.Asn556Asp
Coding: c.1666A>G
MANE Select: NM_001256106
dbSNP: rs145387761
Type: single nucleotide variant
Location: chr1:117018209 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 556: the ig-like c2-type 5 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-asn556asp (accessed [today's date]).

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