Is CD101 p.Met263Lys (c.788T>A) pathogenic?

CD101 p.Met263Lys (c.788T>A) is classified Uncertain significance in CD101 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.0897); Very rare (popmax 0.00267%, afr).

How common is CD101 p.Met263Lys (c.788T>A) in the general population?

CD101 p.Met263Lys (c.788T>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CD101 p.Met263Lys (c.788T>A)?

AlphaMissense predicts likely benign (score 0.0897) — an in-silico prediction, not a clinical call.

CD101 p.Met263Lys

c.788T>A · rs1451142319 · VCV3140269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0897 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0897	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.56	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 1.8	GERP -2.7, phastCons 0.94
Regional constraint	o/e 0.94	unconstrained · MANE · 32 kb · p 0.034 · regional, not allelic
Overall
CADD	7.246	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 0.00267% African / African-American · 2/74,914 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,457
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,078

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.Met263Lys
Coding: c.788T>A
MANE Select: NM_001256106
dbSNP: rs1451142319
Type: single nucleotide variant
Location: chr1:117011913 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.76
Residue 263: 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-met263lys (accessed [today's date]).

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