Is CD2 p.Ser108Leu (c.323C>T) pathogenic?

CD2 p.Ser108Leu (c.323C>T) is classified Uncertain significance in CD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1493); Very rare (popmax 0.00112%, sas).

How common is CD2 p.Ser108Leu (c.323C>T) in the general population?

CD2 p.Ser108Leu (c.323C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

What do computational predictors say about CD2 p.Ser108Leu (c.323C>T)?

AlphaMissense predicts likely benign (score 0.1493) — an in-silico prediction, not a clinical call.

CD2 p.Ser108Leu

c.323C>T · VCV4650494

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1493 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1493	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.2	GERP -4
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.97 · regional, not allelic
Overall
CADD	0.005	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 0.00112% South Asian · 1/89,504 alleles

Overall 6.86e-05% 1/1,456,688 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: CD2
Protein: p.Ser108Leu
Coding: c.323C>T
MANE Select: NM_001767
Type: single nucleotide variant
Location: chr1:116754892 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 7 PDB
Residue 108: a β-strand; the ig-like v-type domain; the 'cd58 binding region 2' region

Full CD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD2 p.Ala270Thr Uncertain significance ★ ⚠ same type
CD2 p.Ala292Ser Uncertain significance ★ ⚠ same type
CD2 p.Ala342Thr Uncertain significance ★ ⚠ same type
CD2 p.Arg129Lys Uncertain significance ★ ⚠ same type
CD2 p.Arg129Trp Uncertain significance ★ ⚠ same type
CD2 p.Arg243Gln Uncertain significance ★ ⚠ same type
CD2 p.Arg243Leu Uncertain significance ★ ⚠ same type
CD2 p.Arg263Gln 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/cd2-p-ser108leu (accessed [today's date]).

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