Is CD2 p.Ser347Phe (c.1040C>T) pathogenic?

CD2 p.Ser347Phe (c.1040C>T) is classified Uncertain significance in CD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: likely benign (0.1258); Very rare (popmax 0.000255%, nfe).

How common is CD2 p.Ser347Phe (c.1040C>T) in the general population?

CD2 p.Ser347Phe (c.1040C>T) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about CD2 p.Ser347Phe (c.1040C>T)?

AlphaMissense predicts likely benign (score 0.1258) — an in-silico prediction, not a clinical call.

CD2 p.Ser347Phe

c.1040C>T · VCV3264761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1258 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1258	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.085	GERP -1.7
Regional constraint	o/e 1.00	unconstrained · MANE · 14 kb · p 0.97 · regional, not allelic
Overall
CADD	12.26	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 0.000255% European (non-Finnish) · 3/1,178,400 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000497% 8/1,609,182 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00626%	15,969
Remaining individualsnot grpmax-eligible	0.00161%	62,220
European (non-Finnish)grpmax	0.000255%	392,801

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser347Phe
Coding: c.1040C>T
MANE Select: NM_001767
Type: single nucleotide variant
Location: chr1:116768767 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.25 · 7 PDB
Residue 347: the 'disordered' 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-ser347phe (accessed [today's date]).

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