Is CD101 p.His177Asp (c.529C>G) pathogenic?

CD101 p.His177Asp (c.529C>G) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.659); Very rare (popmax 0.0011%, sas).

How common is CD101 p.His177Asp (c.529C>G) in the general population?

CD101 p.His177Asp (c.529C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CD101 p.His177Asp (c.529C>G)?

AlphaMissense predicts likely pathogenic (score 0.659) — an in-silico prediction, not a clinical call.

CD101 p.His177Asp

c.529C>G · VCV3997944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.659	likely pathogenic · top 9% in CD101
REVEL	0.504	indeterminate
SaProt	LLR -4.74	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	25.7	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 0.0011% South Asian · 1/91,070 alleles

Overall 6.84e-05% 1/1,461,884 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: CD101
Protein: p.His177Asp
Coding: c.529C>G
MANE Select: NM_001256106
Type: single nucleotide variant
Location: chr1:117011654 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 177: a disulfide bond; the ig-like c2-type 2 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-his177asp (accessed [today's date]).

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